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1. IGLON5 Frequency in Idiopathic REM Sleep Behavior Disorder: A Multicenter Study.

Author: Postuma, Ronald, Vorasoot, Nisa, St Louis, Erik, Pelletier, Amélie, Lim, Miranda, Elliott, Jonathan, Gagnon, Jean-Francois, Gan-Or, Ziv, Forsberg, Leah, Fields, Julie, Ross, Owen, Singer, Wolfgang, Huddleston, Daniel, Bliwise, Donald, Avidan, Alon, Howell, Michael, Schenck, Carlos, McLeland, Jennifer, Davis, Albert, Criswell, Susan, Videnovic, Aleksandar, During, Emmanuel, Miglis, Mitchell, Boeve, Bradley, Ju, Yo-El, and McKeon, Andrew
Subjects: Humans, REM Sleep Behavior Disorder, Male, Female, Autoantibodies, Aged, Cell Adhesion Molecules, Neuronal, Middle Aged, Cohort Studies
Abstract: BACKGROUND AND OBJECTIVES: Idiopathic/isolated REM sleep behavior disorder (iRBD) has been strongly linked to neurodegenerative synucleinopathies such as Parkinson disease, dementia with Lewy bodies, and multiple system atrophy. However, there have been increasing reports of RBD as a presenting feature of serious and treatable autoimmune syndromes, particularly IGLON5. This studys objective was to investigate the frequency of autoantibodies in a large cohort of participants with iRBD. METHODS: Participants were enrolled in the North American Prodromal Synucleinopathy cohort with polysomnography-confirmed iRBD, free of parkinsonism and dementia. Plasma samples were systematically screened for the autoantibodies IGLON5, DPPX, LGI1, and CASPR2 using plasma IgG cell-based assay. Positive or equivocal results were confirmed by repeat testing, plus tissue-based indirect immunofluorescence assay for IGLON5. RESULTS: Of 339 samples analyzed, 3 participants (0.9%) had confirmed positive IGLON5 autoantibodies in the cell-based assay, which were confirmed by the tissue-based assay. An additional participant was positive for CASPR2 with low titer by cell-based assay only (of lower clinical certainty). These cases exhibited a variety of symptoms including dream enactment, cognitive decline, autonomic dysfunction, and motor symptoms. In 1 IGLON5 case and the CASPR2 case, evolution was suggestive of typical synucleinopathy, suggesting the possibility that findings were incidental. However, 2 participants with IGLON5 died before diagnosis was clinically suspected, with a final clinical picture highly suggestive of autoimmune disease. DISCUSSION: Our finding that nearly 1% of a large iRBD cohort may have a serious but potentially treatable autoantibody syndrome has important clinical implications. In particular, it raises the question of whether autoantibody testing for IGLON-5-IgG should be widely implemented for participants with iRBD, considering the difficulty in diagnosis of autoimmune diseases, their response to treatment, and the potential for rapid disease progression. However, any routine testing protocol will also have to consider costs and potential adverse effects of false-positive findings. TRIAL REGISTRATION INFORMATION: NCT03623672.
Published: 2024

2. Comorbid neurotrauma increases neurodegenerative-relevant cognitive, motor, and autonomic dysfunction in patients with rapid eye movement sleep behavior disorder: a substudy of the North American Prodromal Synucleinopathy Consortium.

Author: Elliott, Jonathan, Ligman, Brittany, Bryant-Ekstrand, Mohini, Keil, Allison, Powers, Katherine, Olivo, Cosette, Neilson, Lee, Postuma, Ronald, Pelletier, Amélie, Gagnon, Jean-François, Gan-Or, Ziv, Yu, Eric, Liu, Lang, St Louis, Erik, Forsberg, Leah, Fields, Julie, Ross, Owen, Huddleston, Daniel, Bliwise, Donald, Avidan, Alon, Howell, Michael, Schenck, Carlos, McLeland, Jennifer, Criswell, Susan, Videnovic, Aleksandar, During, Emmanuel, Miglis, Mitchell, Shprecher, David, Lee-Iannotti, Joyce, Boeve, Bradley, Ju, Yo-El, and Lim, Miranda
Subjects: Parkinson’s disease, RBD, REM sleep without atonia, posttraumatic stress disorder, synucleinopathy, trauma-associated sleep disorder, traumatic brain injury, Humans, REM Sleep Behavior Disorder, Male, Female, Middle Aged, Cross-Sectional Studies, Aged, Brain Injuries, Traumatic, Synucleinopathies, Stress Disorders, Post-Traumatic, Prodromal Symptoms, Polysomnography, Comorbidity, Autonomic Nervous System Diseases, Cognitive Dysfunction, Parkinson Disease
Abstract: STUDY OBJECTIVES: Rapid eye movement sleep behavior disorder (RBD) is strongly associated with phenoconversion to an overt synucleinopathy, e.g. Parkinsons disease (PD), Lewy body dementia, and related disorders. Comorbid traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD)-henceforth neurotrauma (NT)-increase the odds of RBD by ~2.5-fold and are associated with an increased rate of service-connected PD in Veterans. Thus, RBD and NT are both independently associated with PD; however, it is unclear how NT influences neurological function in patients with RBD. METHODS: Participants ≥18 years with overnight polysomnogram-confirmed RBD were enrolled between 8/2018 to 4/2021 through the North American Prodromal Synucleinopathy Consortium. Standardized assessments for RBD, TBI, and PTSD history, as well as cognitive, motor, sensory, and autonomic function, were completed. This cross-sectional analysis compared cases (n = 24; RBD + NT) to controls (n = 96; RBD), matched for age (~60 years), sex (15% female), and years of education (~15 years). RESULTS: RBD + NT reported earlier RBD symptom onset (37.5 ± 11.9 vs. 52.2 ± 15.1 years of age) and a more severe RBD phenotype. Similarly, RBD + NT reported more severe anxiety and depression, greater frequency of hypertension, and significantly worse cognitive, motor, and autonomic function compared to RBD. No differences in olfaction or color vision were observed. CONCLUSIONS: This cross-sectional, matched case:control study shows individuals with RBD + NT have significantly worse neurological measures related to common features of an overt synucleinopathy. Confirmatory longitudinal studies are ongoing; however, these results suggest RBD + NT may be associated with more advanced neurological symptoms related to an evolving neurodegenerative process.
Published: 2024

3. Frequency of Orthostatic Hypotension in Isolated REM Sleep Behavior Disorder.

Author: Elliott, Jonathan, Bryant-Ekstrand, Mohini, Keil, Allison, Ligman, Brittany, Lim, Miranda, Zitser, Jennifer, During, Emmanuel, Gagnon, Jean-Francois, St Louis, Erik, Fields, Julie, Huddleston, Daniel, Bliwise, Donald, Avidan, Alon, Schenck, Carlos, McLeland, Jennifer, Criswell, Susan, Davis, Albert, Videnovic, Aleksandar, Lee-Iannotti, Joyce, Postuma, Ronald, Boeve, Bradley, Ju, Yo-El, and Miglis, Mitchell
Subjects: Humans, Male, Female, REM Sleep Behavior Disorder, Hypotension, Orthostatic, Synucleinopathies, Parkinson Disease, Autonomic Nervous System Diseases
Abstract: BACKGROUND AND OBJECTIVES: Although orthostatic hypotension (OH) can be an early feature of autonomic dysfunction in isolated REM sleep behavior disorder (iRBD), no large-scale studies have examined the frequency of OH in iRBD. In this study, we prospectively evaluated the frequency of OH in a large multicenter iRBD cohort. METHODS: Participants 18 years or older with video polysomnogram-confirmed iRBD were enrolled through the North American Prodromal Synucleinopathy consortium. All participants underwent 3-minute orthostatic stand testing to assess the frequency of OH, and a Δ heart rate/Δ systolic blood pressure (ΔHR/ΔSBP) ratio
Published: 2023

4. Baseline characteristics of the North American prodromal Synucleinopathy cohort.

Author: Elliott, Jonathan, Lim, Miranda, Keil, Allison, Postuma, Ronald, Pelletier, Amelie, Gagnon, Jean-François, St Louis, Erik, Forsberg, Leah, Fields, Julie, Huddleston, Daniel, Bliwise, Donald, Avidan, Alon, Howell, Michael, Schenck, Carlos, McLeland, Jennifer, Criswell, Susan, Videnovic, Aleksandar, During, Emmanuel, Miglis, Mitchell, Shprecher, David, Lee-Iannotti, Joyce, Boeve, Bradley, and Ju, Yo-El
Subjects: Female, Humans, Male, Lewy Body Disease, Longitudinal Studies, Multiple System Atrophy, Parkinson Disease, REM Sleep Behavior Disorder, Synucleinopathies
Abstract: OBJECTIVE: Rapid eye movement (REM) sleep behavior disorder (RBD) is widely considered a prodromal synucleinopathy, as most with RBD develop overt synucleinopathy within ~10 years. Accordingly, RBD offers an opportunity to test potential treatments at the earliest stages of synucleinopathy. The North American Prodromal Synucleinopathy (NAPS) Consortium has created a multisite RBD participant, primarily clinic-based cohort to better understand characteristics at diagnosis, and in future work, identify predictors of phenoconversion, develop synucleinopathy biomarkers, and enable early stage clinical trial enrollment. METHODS: Participants ≥18 years of age with overnight polysomnogram-confirmed RBD without Parkinsons disease, dementia, multiple system atrophy, or narcolepsy were enrolled from nine sites across North America (8/2018 to 4/2021). Data collection included family/personal history of RBD and standardized assessments of cognitive, motor, sensory, and autonomic function. RESULTS: Outcomes are primarily reported based on sex (361 total: n = 295 male, n = 66 female), and secondarily based on history of antidepressant use (n = 200 with, n = 154 without; with correction for sex differences) and based on extent of synucleinopathy burden (n = 56 defined as isolated RBD, n = 305 defined as RBD+ [i.e., exhibiting ≥1 abnormality]). Overall, these participants commonly demonstrated abnormalities in global cognition (MoCA; 38%), motor function (alternate tap test; 48%), sensory (BSIT; 57%), autonomic function (orthostatic hypotension, 38.8%), and anxiety/depression (BAI and PHQ-9; 39.3% and 31%, respectively). INTERPRETATION: These RBD participants, assessed with extensive history, demographic, cognitive, motor, sensory, and autonomic function demonstrated a lack of sex differences and high frequency of concomitant neurological abnormalities. These participants will be valuable for future longitudinal study and neuroprotective clinical trials.
Published: 2023

5. Cognitive Change After Cardiac Surgery Versus Cardiac Catheterization: A Population-Based Study

Author: Whitlock, Elizabeth L, Diaz-Ramirez, L Grisell, Smith, Alexander K, Boscardin, W John, Avidan, Michael S, and Glymour, M Maria
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Clinical Sciences, Aging, Cardiovascular, Basic Behavioral and Social Science, Patient Safety, Heart Disease, Behavioral and Social Science, Clinical Research, Age Distribution, Aged, Aged, 80 and over, Analysis of Variance, Angioplasty, Balloon, Coronary, Cardiac Catheterization, Cognition Disorders, Coronary Artery Bypass, Coronary Artery Disease, Female, Humans, Independent Living, Logistic Models, Longitudinal Studies, Male, Middle Aged, Neuropsychological Tests, Prevalence, Prognosis, Retrospective Studies, Severity of Illness Index, Sex Distribution, Surveys and Questionnaires, Cardiorespiratory Medicine and Haematology, Respiratory System, Cardiovascular medicine and haematology, Clinical sciences
Abstract: BackgroundDespite concern that cardiac surgery may adversely affect cognition, little evidence is available from population-based studies using presurgery data. With the use of the Health and Retirement Study, we compared memory change after participant-reported cardiac catheterization or cardiac surgery.MethodsParticipants were community-dwelling adults aged 65 years and older who self-reported cardiac catheterization or "heart surgery" at any biennial Health and Retirement Study interview between 2000 and 2014. Participants may have undergone the index procedure any time in the preceding 2 years. We modeled preprocedure to postprocedure change in composite memory score, derived from objective memory testing, using linear mixed effects models. We modeled postprocedure subjective memory decline with logistic regression. To quantify clinical relevance, we used the predicted memory change to estimate impact on ability to manage medications and finances independently.ResultsOf 3,105 participants, 1,921 (62%) underwent catheterization and 1,184 (38%) underwent operation. In adjusted analyses, surgery participants had little difference in preprocedure to postprocedure memory change compared with participants undergoing cardiac catheterization (-0.021 memory units; 95% confidence interval: -0.046 to 0.005 memory units, p = 0.12). If the relationship were causal, the point estimate for memory decline would confer an absolute 0.26% or 0.19% decrease in ability to manage finances or medications, respectively, corresponding to 4.6 additional months of cognitive aging. Cardiac surgery was not associated with subjective memory decline (adjusted odds ratio 0.93, 95% confidence interval: 0.74 to 1.18).ConclusionsIn this large, population-based cohort, memory declines after heart surgery and cardiac catheterization were similar. These findings suggest intermediate-term population-level adverse cognitive effects of cardiac surgery, if any, are likely subtle.
Published: 2019

6. Sleep Disorders in Neurologic Practice A Case-based Approach

Author: Panossian, Lori Ani and Avidan, Alon Y
Subjects: Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Behavioral and Social Science, Health Services, Brain Disorders, Neurosciences, Mental Health, Clinical Research, Sleep Research, Mental health, Adult, Aged, Aged, 80 and over, Female, Humans, Male, Middle Aged, Nervous System Diseases, Sleep Wake Disorders, Sleep disorders, Narcolepsy, Restless leg syndrome, Sleep apnea, REM sleep behavior disorder, Insomnia, Circadian rhythm disorders, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract: Sleep disorders are common in neurology practice, but are often undiagnosed and untreated. Specific patient cohorts, such as older adults, patients residing in nursing homes, and patients with underlying chronic neurologic and psychiatric disorders, are at particular risk. If these sleep problems are not properly evaluated and managed the patient may experience exacerbation of the underlying neurologic disorder. This article highlights some of the key sleep disorders relevant to practicing neurologists, emphasizing hypersomnolence, insomnia, and sleep-related movement disorders in the setting of neurologic disorders to enhance the tools available for evaluation, and discusses management strategies.
Published: 2016

7. Protocol for the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) study: a pragmatic, randomised clinical trial.

Author: Wildes, TS, Winter, AC, Maybrier, HR, Mickle, AM, Lenze, EJ, Stark, S, Lin, N, Inouye, SK, Schmitt, EM, McKinnon, SL, Muench, MR, Murphy, MR, Upadhyayula, RT, Fritz, BA, Escallier, KE, Apakama, GP, Emmert, DA, Graetz, TJ, Stevens, TW, Palanca, BJ, Hueneke, R, Melby, S, Torres, B, Leung, JM, Jacobsohn, E, and Avidan, MS
Subjects: Humans, Delirium, Postoperative Complications, Electroencephalography, Monitoring, Physiologic, Length of Stay, Anesthesia, General, Regression Analysis, Accidental Falls, Research Design, Quality of Life, Aged, Aged, 80 and over, Middle Aged, United States, Female, Male, Practice Guidelines as Topic, ANAESTHETICS, EDUCATION & TRAINING, GERIATRIC MEDICINE, Monitoring, Physiologic, Anesthesia, General, and over, Clinical Sciences, Public Health and Health Services, Other Medical and Health Sciences
Abstract: IntroductionPostoperative delirium, arbitrarily defined as occurring within 5 days of surgery, affects up to 50% of patients older than 60 after a major operation. This geriatric syndrome is associated with longer intensive care unit and hospital stay, readmission, persistent cognitive deterioration and mortality. No effective preventive methods have been identified, but preliminary evidence suggests that EEG monitoring during general anaesthesia, by facilitating reduced anaesthetic exposure and EEG suppression, might decrease incident postoperative delirium. This study hypothesises that EEG-guidance of anaesthetic administration prevents postoperative delirium and downstream sequelae, including falls and decreased quality of life.Methods and analysisThis is a 1232 patient, block-randomised, double-blinded, comparative effectiveness trial. Patients older than 60, undergoing volatile agent-based general anaesthesia for major surgery, are eligible. Patients are randomised to 1 of 2 anaesthetic approaches. One group receives general anaesthesia with clinicians blinded to EEG monitoring. The other group receives EEG-guidance of anaesthetic agent administration. The outcomes of postoperative delirium (≤5 days), falls at 1 and 12 months and health-related quality of life at 1 and 12 months will be compared between groups. Postoperative delirium is assessed with the confusion assessment method, falls with ProFaNE consensus questions and quality of life with the Veteran's RAND 12-item Health Survey. The intention-to-treat principle will be followed for all analyses. Differences between groups will be presented with 95% CIs and will be considered statistically significant at a two-sided p
Published: 2016

8. Postoperative Delirium in a Substudy of Cardiothoracic Surgical Patients in the BAG-RECALL Clinical Trial

Author: Whitlock, Elizabeth L, Torres, Brian A, Lin, Nan, Helsten, Daniel L, Nadelson, Molly R, Mashour, George A, and Avidan, Michael S
Subjects: Clinical Trials and Supportive Activities, Mental Health, Patient Safety, Clinical Research, Cardiovascular, Aged, Anesthesia, General, Anesthetics, Bayes Theorem, Cardiac Surgical Procedures, Confidence Intervals, Confusion, Consciousness Monitors, Delirium, Female, Humans, Intraoperative Period, Length of Stay, Logistic Models, Male, Middle Aged, Neuropsychological Tests, Postoperative Complications, Predictive Value of Tests, Thoracic Surgical Procedures, Treatment Outcome, Clinical Sciences, Neurosciences, Anesthesiology
Abstract: BackgroundPostoperative delirium in the intensive care unit (ICU) is a frequent complication after cardiac or thoracic surgery and is associated with increased morbidity and mortality.MethodsIn this single-center substudy of the BAG-RECALL trial (NCT00682825), we screened patients after cardiac or thoracic surgery in the ICU twice daily for delirium using the Confusion Assessment Method for the ICU. The primary outcome was the incidence of delirium in patients who had been randomized to intraoperative Bispectral Index (BIS)-guided and end-tidal anesthetic concentration-guided depth of anesthesia protocols. As a secondary analysis, a Bayesian stochastic search variable selection strategy was used to rank a field of candidate risk factors for delirium, followed by binary logistic regression.ResultsOf 310 patients assessed, 28 of 149 (18.8%) in the BIS group and 45 of 161 (28.0%) in the end-tidal anesthetic concentration group developed postoperative delirium in the ICU (odds ratio 0.60, 95% confidence interval, 0.35-1.02, P= 0.058). Low average volatile anesthetic dose, intraoperative transfusion, ASA physical status, and European System for Cardiac Operative Risk Evaluation were identified as independent predictors of delirium.ConclusionsA larger randomized study should determine whether brain monitoring with BIS or an alternative method decreases delirium after cardiac or thoracic surgery. The association between low anesthetic concentration and delirium is a surprising finding and could reflect that patients with poor health are both more sensitive to the effects of volatile anesthetic drugs and are also more likely to develop postoperative delirium. Investigation of candidate methods to prevent delirium should be prioritized in view of the established association between postoperative delirium and adverse patient outcomes.
Published: 2014

9. The Effects of Intraoperative Caffeine on Postoperative Opioid Consumption and Related Outcomes After Laparoscopic Surgery: A Randomized Controlled Trial

Author: Alexander Tsodikov, Joseph Brooks, Graciela Mentz, Michael S. Avidan, Giancarlo Vanini, Duan Li, Daniel J. Clauw, Phillip E. Vlisides, Aleda Leis, Amy M. McKinney, Mackenzie Zierau, Jacqueline Ragheb, and George A. Mashour
Subjects: Adult, Male, Placebo, Article, law.invention, chemistry.chemical_compound, Double-Blind Method, Randomized controlled trial, Interquartile range, law, Caffeine, Humans, Medicine, Longitudinal Studies, Adverse effect, Aged, Pain Measurement, Pain, Postoperative, Intraoperative Care, business.industry, Middle Aged, Analgesics, Opioid, Treatment Outcome, Anesthesiology and Pain Medicine, chemistry, Opioid, Caffeine citrate, Anesthesia, Anxiety, Central Nervous System Stimulants, Female, Laparoscopy, medicine.symptom, business, medicine.drug
Abstract: Background Surgical patients are vulnerable to opioid dependency and related risks. Clinical-translational data suggest that caffeine may enhance postoperative analgesia. This trial tested the hypothesis that intraoperative caffeine would reduce postoperative opioid consumption. The secondary objective was to assess whether caffeine improves neuropsychological recovery postoperatively. Methods This was a single-center, randomized, placebo-controlled trial. Participants, clinicians, research teams, and data analysts were all blinded to the intervention. Adult (≥18 years old) surgical patients (n = 65) presenting for laparoscopic colorectal and gastrointestinal surgery were randomized to an intravenous caffeine citrate infusion (200 mg) or dextrose 5% in water (40 mL) during surgical closure. The primary outcome was cumulative opioid consumption through postoperative day 3. Secondary outcomes included subjective pain reporting, observer-reported pain, delirium, Trail Making Test performance, depression and anxiety screens, and affect scores. Adverse events were reported, and hemodynamic profiles were also compared between the groups. Results Sixty patients were included in the final analysis, with 30 randomized to each group. The median (interquartile range) cumulative opioid consumption (oral morphine equivalents, milligrams) was 77 mg (33-182 mg) for caffeine and 51 mg (15-117 mg) for placebo (estimated difference, 55 mg; 95% confidence interval [CI], -9 to 118; P = .092). After post hoc adjustment for baseline imbalances, caffeine was associated with increased opioid consumption (87 mg; 95% CI, 26-148; P = .005). There were otherwise no differences in prespecified pain or neuropsychological outcomes between the groups. No major adverse events were reported in relation to caffeine, and no major hemodynamic perturbations were observed with caffeine administration. Conclusions Caffeine appears unlikely to reduce early postoperative opioid consumption. Caffeine otherwise appears well tolerated during anesthetic emergence.
Published: 2021
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10. The ED-AWARENESS Study: A Prospective, Observational Cohort Study of Awareness With Paralysis in Mechanically Ventilated Patients Admitted From the Emergency Department

Author: Winston Winkler, Anne M. Drewry, Marin H. Kollef, Yan Yan, Ryan D Pappal, Brian M. Fuller, Nicholas M. Mohr, Michael S. Avidan, Brian W. Roberts, Brian Wessman, and Enyo Ablordeppey
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Population, Anesthesia, General, 03 medical and health sciences, 0302 clinical medicine, Surveys and Questionnaires, Paralysis, medicine, Humans, Prospective Studies, 030212 general & internal medicine, education, Prospective cohort study, Aged, Mechanical ventilation, education.field_of_study, business.industry, 030208 emergency & critical care medicine, Odds ratio, Emergency department, Awareness, Middle Aged, Respiration, Artificial, Case-Control Studies, Emergency medicine, Cohort, Emergency Medicine, Female, medicine.symptom, business, Cohort study
Abstract: Study objective Awareness with paralysis is a devastating complication for patients receiving mechanical ventilation and risks long-term psychological morbidity. Data from the emergency department (ED) demonstrate a high rate of longer-acting neuromuscular blocking agent use, delayed analgosedation, and a lack of sedation depth monitoring. These practices are discordant with recommendations for preventing awareness with paralysis. Despite this, awareness with paralysis has not been rigorously studied in the ED population. Our objective is to assess the prevalence of awareness with paralysis in ED patients receiving mechanical ventilation. Methods This was a single-center, prospective, observational cohort study on 383 mechanically ventilated ED patients. After extubation, we assessed patients for awareness with paralysis by using the modified Brice questionnaire. Three expert reviewers independently adjudicated awareness with paralysis. We report the prevalence of awareness with paralysis (primary outcome); the secondary outcome was perceived threat, a mediator for development of posttraumatic stress disorder. Results The prevalence of awareness with paralysis was 2.6% (10/383). Exposure to rocuronium at any point in the ED was significantly different between patients who experienced awareness with paralysis (70%) versus the rest of the cohort (31.4%) (unadjusted odds ratio 5.1; 95% confidence interval 1.30 to 20.1). Patients experiencing awareness with paralysis had higher mean values on the threat perception scale, denoting a higher degree of perceived threat, compared with patients who did not experience awareness with paralysis (13.4 [SD 7.7] versus 8.5 [SD 6.2]; mean difference 4.9; 95% confidence interval 0.94 to 8.8). Conclusion Awareness with paralysis occurs in a significant minority of ED patients who receive mechanical ventilation. Potential associations of awareness with paralysis with ED care and increased perceived threat warrant further evaluation.
Published: 2021
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11. Repurposing Propofol as a Prognostic Probe for Return of Consciousness

Author: George A. Mashour and Michael S. Avidan
Subjects: Pulmonary and Respiratory Medicine, Adult, Male, Adolescent, Consciousness, media_common.quotation_subject, Electroencephalography, Critical Care and Intensive Care Medicine, Young Adult, Predictive Value of Tests, medicine, Humans, Coma, Propofol, Repurposing, media_common, Aged, medicine.diagnostic_test, business.industry, Editorials, Recovery of Function, Middle Aged, Prognosis, Anesthesia, Brain Injuries, Anesthesia Recovery Period, Consciousness Disorders, Female, medicine.symptom, business, Anesthetics, Intravenous, medicine.drug, Forecasting
Published: 2021

12. Surgical Complications in Older Adults Predict Decline in Self-Perceived Cognitive Function in the Ensuing Year: A Cohort Study

Author: Michael S. Avidan, Eric J. Lenze, Thomas George Kannampallil, Joanna Abraham, Katherine J. Holzer, Uzma Naim, and Simon Haroutounian
Subjects: Male, Pediatrics, medicine.medical_specialty, Longitudinal study, Activities of daily living, Article, 03 medical and health sciences, Cognition, Postoperative Complications, 0302 clinical medicine, Activities of Daily Living, Humans, Medicine, Cognitive Dysfunction, Longitudinal Studies, Prospective Studies, Cognitive skill, Cognitive decline, Aged, 030214 geriatrics, business.industry, Perioperative, Confidence interval, Psychiatry and Mental health, Female, Self Report, Geriatrics and Gerontology, business, Complication, Cohort study
Abstract: Background Surgical complications are common among older adults and are potential indicators of poorer long-term outcomes. The authors examined the effects of in-hospital complications on changes in older adults’ self-perceived cognitive function in the year after surgery. Method The authors conducted a prospective longitudinal study with 2,155 older adults (age ≥ 65) undergoing surgery, investigating the association between self-reported, in-hospital complications after surgery and Patient-Reported Outcomes Measurement Information System Applied Cognition-Abilities survey (4 items, cognitive function) at 30 days and 1 year after surgery. Surveys were scored on a continuous scale of 0–100, with higher scores representing better self-perceived cognitive functioning. Patient characteristics including demographics, type of complications, surgery type, pain, and activities of daily living were also collected. Results Having one in-hospital complication was associated with a decrease of 1.79 points (95% confidence interval (CI): −2.78, −0.80), indicating lower self-perceived cognitive functioning at 1 year after surgery; having two or more in-hospital complications was associated with 2.82 point (95% CI: −4.50, −1.15) decrease at 1 year after surgery. Models specific to complication type indicated that respiratory [−3.04, (95% CI: −5.50, −0.57)], neural [−2.11, (95% CI: −3.97, −0.25)], and general complications [−2.39, (95% CI: −3.51, −1.28)] were associated with statistically significant decreases in cognitive function. Discussion Older surgical patients who suffer in-hospital complications show greater decline in self-perceived cognitive function during the ensuing year. Geriatric specialists may be able to intervene in the immediate perioperative period to reduce complications and possibly mitigate cognitive decline among older adults.
Published: 2021
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13. A Qualitative Study of Perioperative Depression and Anxiety in Older Adults

Author: Ana A. Baumann, Thomas George Kannampallil, Eric J. Lenze, Michael S. Avidan, Alicia Meng, Mary C. Politi, Joanna Abraham, and Susan Siraco
Subjects: Male, medicine.medical_specialty, Population, Psychological intervention, Anxiety, medicine, Humans, Precision Medicine, Perioperative Period, education, Intersectoral Collaboration, Qualitative Research, Aged, education.field_of_study, Depression, business.industry, Perioperative, Mental health, Psychiatry and Mental health, Family medicine, Female, Geriatrics and Gerontology, medicine.symptom, Thematic analysis, business, Neurocognitive, Qualitative research
Abstract: Objective We had three aims 1) understand barriers to perioperative management of anxiety and depression in older surgical patients; 2) identify preferences and requirements for interventions to manage their anxiety and depression; and 3) explore the feasibility of implementing such interventions in perioperative care. Design A qualitative study using semistructured interviews was conducted. Setting Participants were recruited at a large academic medical center. Participants We interviewed older surgical patients and clinicians to characterize their perspectives on management of anxiety and depression symptoms, with emphasis on patient needs, barriers, and potential interventions to address these needs. Measurements We used the Consolidated Framework for Intervention Research to guide the development of interview questions related to intervention implementation feasibility. Thematic analysis was used to analyze interview responses. Results Forty semistructured interviews were conducted. Key barriers for perioperative management of depression and anxiety included fear of surgery, acute pain, postoperative neurocognitive disorders, limited understanding of what to expect regarding surgery and recovery, and overwhelmingly complex medication management. Patients and clinicians suggested that a bundled mental health management intervention targeted for older surgical patient population comprised of behavioral and pharmacologic strategies can help mitigate anxiety and depression symptoms during the perioperative period. Clinicians emphasized the need for a collaborative engagement strategy that includes multiple stakeholders in the design, planning, and implementation of such an intevention. Conclusion New care models need to be developed to integrate mental health care into the current perioperative care practice.
Published: 2020
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14. Cognitive flexibility and persistent post-surgical pain: the FLEXCAPP prospective observational study

Author: Simon Haroutounian, Michael M. Bottros, Michael S. Avidan, Beverly J. Field, Aaron Steinberg, Marilee A. Fisher, Molly R. Vila, Marko S. Todorovic, and Cynthia Y. Tang
Subjects: Adult, Male, medicine.medical_specialty, medicine.medical_treatment, Trail Making Test, Neuropsychological Tests, Sensitivity and Specificity, Executive Function, Risk Factors, medicine, Humans, Prospective Studies, Arthroplasty, Replacement, Knee, Mastectomy, Aged, Pain, Postoperative, business.industry, Chronic pain, Cognitive flexibility, Perioperative, Middle Aged, Thoracic Surgical Procedures, medicine.disease, Arthroplasty, Clinical trial, Anesthesiology and Pain Medicine, Physical therapy, Female, Observational study, Chronic Pain, Cognition Disorders, business, Follow-Up Studies, Stroop effect
Abstract: Background Impaired performance on tasks assessing executive function has been linked to chronic pain. We hypothesised that poor performance on tests assessing the ability to adjust thinking in response to changing environmental stimuli (cognitive flexibility) would be associated with persistent post-surgical pain. Methods We conducted a single-centre prospective observational study in two perioperative cohorts: patients undergoing total knee arthroplasty or noncardiac chest surgical procedures. The co-primary outcome measures compared preoperative performance on the Trail Making Test and the colour–word matching Stroop test between patients who developed persistent post-surgical pain and those who did not. Secondary outcome measures included the associations between these test scores and pain severity at 6 months. Results Of 300 participants enrolled, 198 provided 6 month follow-up data. There were no significant differences in preoperative Trail Making Test B minus A times (33 vs 34 s; P=0.59) or Stroop interference T-scores (47th vs 48th percentile; P=0.50) between patients with and without persistent post-surgical pain (primary outcome). Of those who reported persistent post-surgical pain, poorer baseline performance on the colour–word matching Stroop test was associated with higher pain scores at 6 months in both knee arthroplasty (r=–0.32; P=0.04) and chest (r=–0.44; P=0.02) surgeries (secondary outcome). Conclusions Preoperative cognitive flexibility test performance was not predictive of overall persistent post-surgical pain incidence 6 months after surgery. However, poor performance on the colour–word matching Stroop test was independently associated with more severe persistent post-surgical pain in both cohorts. Clinical trial registration NCT02579538.
Published: 2020
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15. From a deep learning model back to the brain—Identifying regional predictors and their relation to aging

Author: Galia Avidan, Tammy Riklin Raviv, Gideon Rosenthal, Ilan Shelef, and Gidon Levakov
Subjects: Adult, Male, Aging, Multivariate statistics, Adolescent, Computer science, Datasets as Topic, Inference, computer.software_genre, Convolutional neural network, 050105 experimental psychology, Correlation, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Neuroimaging, Voxel, convolutional neural networks, Humans, 0501 psychology and cognitive sciences, Radiology, Nuclear Medicine and imaging, Child, Research Articles, Aged, Interpretability, Aged, 80 and over, neuroimaging, Radiological and Ultrasound Technology, business.industry, Deep learning, 05 social sciences, Age Factors, Brain, deep learning, Pattern recognition, Middle Aged, Magnetic Resonance Imaging, Neurology, Child, Preschool, Female, brain aging, Neurology (clinical), Artificial intelligence, Anatomy, interpretability, business, computer, 030217 neurology & neurosurgery, Research Article
Abstract: We present a Deep Learning framework for the prediction of chronological age from structural magnetic resonance imaging scans. Previous findings associate increased brain age with neurodegenerative diseases and higher mortality rates. However, the importance of brain age prediction goes beyond serving as biomarkers for neurological disorders. Specifically, utilizing convolutional neural network (CNN) analysis to identify brain regions contributing to the prediction can shed light on the complex multivariate process of brain aging. Previous work examined methods to attribute pixel/voxel‐wise contributions to the prediction in a single image, resulting in “explanation maps” that were found noisy and unreliable. To address this problem, we developed an inference scheme for combining these maps across subjects, thus creating a population‐based, rather than a subject‐specific map. We applied this method to a CNN ensemble trained on predicting subjects' age from raw T1 brain images in a lifespan sample of 10,176 subjects. Evaluating the model on an untouched test set resulted in mean absolute error of 3.07 years and a correlation between chronological and predicted age of r = 0.98. Using the inference method, we revealed that cavities containing cerebrospinal fluid, previously found as general atrophy markers, had the highest contribution for age prediction. Comparing maps derived from different models within the ensemble allowed to assess differences and similarities in brain regions utilized by the model. We showed that this method substantially increased the replicability of explanation maps, converged with results from voxel‐based morphometry age studies and highlighted brain regions whose volumetric variability correlated the most with the prediction error., The current work has two main contributions, a CNN ensemble shown to estimate “brain age” from structural MRI with a mean absolute error of ~3.1 years, and a novel scheme highlightighting brain regions contributing to the age prediction. This scheme results in explanation maps showing consistency with the literature, and as sample size increases, these maps show higher inter‐sample replicability. Cerebrospinal fluid cavities, possibly reflecting general atrophy, were found as a prominent aging biomarker.
Published: 2020
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16. Association between postoperative complications and lingering post-surgical pain: an observational cohort study

Author: Caitlin Curcuru, Troy S. Wildes, Arbi Ben Abdallah, Simon Haroutounian, Sherry L. McKinnon, Alex Kronzer, Bruce L. Hall, Mark D. Willingham, Govind Rangrass, Michael S. Avidan, Daniel L. Helsten, and Anshuman Sharma
Subjects: Male, Pain, Postoperative, medicine.medical_specialty, Missouri, business.industry, Confounding, Postoperative complication, Comorbidity, Odds ratio, Middle Aged, Confidence interval, Cohort Studies, Postoperative Complications, Anesthesiology and Pain Medicine, Internal medicine, Cohort, medicine, Humans, Female, Chronic Pain, Complication, Elective Surgical Procedure, business, Aged, Cohort study
Abstract: Background Post-surgical pain that lingers beyond the initial few-week period of tissue healing is a major predictor of pain chronification, which leads to substantial disability and new persistent opioid analgesic use. We investigated whether postoperative medical complications increase the risk of lingering post-surgical pain. Methods The study population consisted of patients undergoing diverse elective surgical procedures in an academic referral centre in the USA, between September 2013 and May 2017. Multivariable logistic regression, adjusting for confounding variables and patient-specific risk factors, was used to test for an independent association between any major postoperative complication and functionally limiting lingering pain 1–3 months after surgery, as obtained from patient self-reports. Results The cohort included 11 986 adult surgical patients; 10 562 with complete data. At least one complication (cardiovascular, respiratory, renal/gastrointestinal, wound, thrombotic, or neural) was reported by 13.3% (95% confidence interval: 12.7–14.0) of patients, and 19.7% (19.0–20.5%) reported functionally limiting lingering post-surgical pain. After adjusting for known risk factors, the patients were twice as likely (odds ratio: 2.04; 1.78–2.35) to report lingering post-surgical pain if they also self-reported a postoperative complication. Experiencing a complication was also independently predictive of lingering post-surgical pain (odds ratio: 1.95; 1.26–3.04) when complication data were extracted from the National Surgical Quality Improvement Program registry, instead of being obtained from patient self-report. Conclusions Medical complications were associated with a two-fold increase in functionally limiting pain 1–3 months after surgery. Understanding the mechanisms that link complications to pathological persistence of pain could help develop future approaches to prevent persistent post-surgical pain.
Published: 2020
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17. [INTRAOPERATIVE RADIOTHERAPY FOR EARLY BREAST CANCER - THE SHEBA EXPERIENCE AND EARLY OUTCOMES]

Author: Vered, Avidan-Noy, Orit, Keidar-Person, Shira, Galper, Zvi, Symon, Miri, Sklair-Levy, Amina, Issa, Aviram, Nissan, and Dov, Zippel
Subjects: Treatment Outcome, Radiotherapy, Humans, Breast Neoplasms, Electrons, Female, Neoplasm Recurrence, Local, Mastectomy
Abstract: This study presents our experience with Intra-Operative Electron Radio-Therapy (IOeRT) using a mobile linear accelerator at the Sheba Medical Center.Intraoperative radiotherapy is an alternative approach of partial breast irradiation for patients with early breast cancer and low risk for local recurrence who are undergoing breast conservation surgery.Patients were selected by a multidisciplinary team according to ASTRO\GEC-ESTRO guidelines for partial breast irradiation. IOeRT was administered using SIT LIAC HWL®.A total of 28 patients were referred for breast conservation surgery and IOeRT between 8/2019 and 10/2020; 27/28 received IOeRT. In one patient, radiation was aborted due to anaphylactic shock in response to patent blue dye injected for sentinel node identification. Larger than usual seroma were reported on the first post-operative visit in all patients, and regressed spontaneously in 3-6 months. Infected seroma developed post-operatively in 5 patients, requiring surgical drainage in 2 patients. Final pathology matched the preoperative biopsy. There were no cases of pathology upstaging requiring additional adjuvant irradiation or chemotherapy. The patient who did not receive IOeRT was treated with adjuvant external radiotherapy.IOeRT is a safe alternative to partial breast irradiation, with a slight increase of postoperative infection rate.
Published: 2022

18. Long-Term Follow-up and Predictors of Complicated Disease Behavior in Pediatric Crohn's Disease Patients

Author: Michal Kori, Maya Avidan, and Chani Topf-Olivestone
Subjects: Male, Adolescent, Crohn Disease, Albumins, Pediatrics, Perinatology and Child Health, Gastroenterology, Disease Progression, Humans, Female, Constriction, Pathologic, Child, Follow-Up Studies
Abstract: Identifying predictors of inflammatory bowel disease (IBD) outcome in order to optimize individual patient management in has become an important goal. We aimed to describe the long-term outcome of pediatric Crohn disease (CD) patients and identify risk factors for complicated behavior.Pediatric CD patients diagnosed between 1998 and 2014, with long-term follow-up were included. Baseline data; age, gender, weight/height/BMI percentiles, and family history of IBD. Disease characteristics (Paris classification), laboratory testing, imaging and treatment were documented. Outcome data; evidence of stricturing or penetrating disease, hospitalizations, surgical intervention, malignancies, and mortality.Of 93 patients included, mean age at diagnosis 13.5 (±3.2), 51 (55%) male, median follow-up 10.3 years (±4 SD(. Disease location at diagnosis: 29 (31.2%) distal ileum, 17 (18.3%) colonic, 40 (43.0%) ileo-colonic. Seven (7.5%) had upper gastrointestinal and 36 (38.7%) perianal involvement. Behavior at diagnosis, 68 (73.1%) inflammatory (B1), and 25 (26.9%) complicated [(B2 (stricturing) and/or B3 (penetrating)]. Twenty (23.2%) of B1 evolved to B2 and/or B3, thus by the end of follow-up 45 (48.4%) had complicated behavior. Sixty-seven (72%) were hospitalized, 20 (21.5%) underwent surgery, two developed malignancy with no mortalities. In a logistic regression model, growth delay (hazard ratio [HR], 5.02 [1.10-22.85], P = 0.037) and low albumin levels (HR, 3.97 [1.32-11.97], P = 0.014) at diagnosis were predictors of complicated disease in adulthood.Over a quarter of pediatric Crohn disease patients present with complicated behavior. During follow-up another quarter progress to complicated disease behavior. Delayed growth and low albumin at diagnosis predict progression.
Published: 2022

19. I-CARE, a European Prospective Cohort Study Assessing Safety and Effectiveness of Biologics in Inflammatory Bowel Disease

Author: Laurent Peyrin-Biroulet, Jean-François Rahier, Julien Kirchgesner, Vered Abitbol, Sebastian Shaji, Alessandro Armuzzi, Konstantinos Karmiris, Javier P. Gisbert, Peter Bossuyt, Ulf Helwig, Johan Burisch, Henit Yanai, Glen A. Doherty, Fernando Magro, Tamás Molnar, Mark Löwenberg, Jonas Halfvarson, Edyta Zagorowicz, Hélène Rousseau, Cédric Baumann, Filip Baert, Laurent Beaugerie, Jean-Marc Gornet, Jean-Marie Reimund, Xavier Hebuterne, Aurélien Amiot, Franco Armelao, Pierre Blanc, Claudio Papi, Guillaume Pineton De Chambrun, Xavier Roblin, null Chu, Sohail Shariq, Nikolaos Viazis, Jimmy Limdi, Piotr Eder H, Georgios Michalopoulos, Andrew Bell, Livia Biancone, Marie Dewitte, Zia Mazhar, Denis Franchimont, Stephane Nancey, Gilles Macaigne, Maria Beatrice Principi, Mathurin Fumery, Gareth Parkes, Jean-Christophe Valats, Glen Doherty, Guillaume Bouguen, Hersin Tsai, Mohsin Gangi, Natalia Pedersen, Frédéric Heluwaert, Richard Shenderey, Sebastian Zeissig, Jeffrey Butterworth, Fabiana Castiglione, Lynsey Corless, Camille Zallot, Salil Singh, Sunil Sonwalkar, Elizabeth Clayton, Deven Vani, Guy Bellaiche, Martine De Vos, Uri Kopylov, Triana Lobaton, Christophe Locher, Gerassimos Mantzaris, George Abouda, Katie Smith, Michael Sprakes, Angeliki Theodoropoulou, Emma Wesley, Joëlle Bonnet, David Elphick, Cyrielle Gilletta, John Gordon, David Laharie, Antoine Nakad, Ambrogio Orlando, Patrick Dubois, Peter Hasselblatt, Christophe Michiels, Cathryn Preston, Anca Staicu, Lucine Vuitton, Mehdi Kaassis, Ally Speight, Deb Ghosh, Nicolas Mathieu, Anne-Laure Pelletier, Anne Phillips, Romain Altwegg, Irit Avni, null biron, Jonathon Landy, Maria Nachury, Achuth Shenoy, Caroline Trang, Georgios Bamias, Klaudia Farkas, Christian Maaser, Ariella Shitrit, Britta Siegmund, Jérôme Filippi, Colm O'morain, Laurent Costes, David Hobday, Zoltán Szepes, Emma Calabrese, Helen Dallal, Michael Fung, Arvind Ramadas, Bijay Baburajan, Konrad Koss, Christophe Barberis, Anthony Buisson, Morgane Amil, Paola Balestrieri, Matthew Johnson, Maria Tzouvala, Stéphanie Viennot, Ferenc Nagy, Nick Thompson, Laurent Alric, Sunil Samuel, Anne Bourrier, Elise Chanteloup, Emilie Del Tedesco, Marcus Harbord, Alan Lobo, Sally Myers, Richard Pollok, Tariq Ahmad, Rakesh Chaudhary, Christos Karakoidas, Ashraf Soliman, Carmen Stefanescu, Georgios Theocharis, Stijn Vanden Branden, Belén Beltran, Yoram Bouhnik, Arnaud Bourreille, Joana Branco, Ben Colleypriest, Rami Eliakim, Paul Knight, Aoibhlinn O'toole, Virgina Robles, Konstantinos Triantafyllou, Marta Maia Bosca, Guy Lambrecht, Lucia Marquez Mosquera, Simon Panter, Aikaterini Pappa, Marion Simon, Ganesh Sivaji, Christophe Bellanger, Arthur Belle, Natalia Borruel, Laurence Egan, Harald Peeters, Daniel Sharpstone, Ramesh Arasaradnam, José Manuel Benitez, Jens Frederik Dahlerup, Olga Giouleme, Miguel Minguez, Eftychia Tsironi, Angela Variola, Patrick Allen, Lucille Boivineau, Andy Cole, Nina Dib, Fernando Gomollon, Richard Johnston, Konstantinos Katsanos, Nick Kennedy, Marianne Kiszka-Kanowitz, Ignacio Marin-Jimenez, Pál Miheller, Pilar Nos, Othman Saraj, Lars Vinter-Jensen, Eran Zittan, Clotilde Baudry, Xavier Calvet, Marie-Christine Cazelles-Boudier, Jean-Louis Coenegrachts, Garret Cullen, Marco Daperno, Anjan Dhar, Romain Gerard, Nanna Jensen, Nitsan Maharshak, Mark Mcalindon, Simon Mcloughlin, Miles Parkes, Kamal Patel, Armando Peixoto, Dimitrios Polymeros, Francisco Portela, Rodolfo Rocca, Philippe Seksik, Sreedhar Subramanian, Ruth Tennenbaum, Raja Atreya, Oliver Bachmann, Arthur Berger, Renáta Bor, Maire Buckley, Daniel Carpio, María Chaparro, Francesco Costa, Eugeni Domenech, Maria Esteve, Stephen Foley, Jordi Guardiola, Ioannis Koutroubakis, Tanja Kuehbacher, Cécilia Landman, Alessandro Lavagna, Noemí Manceñido, Míriam Mañosa, Maria Dolores Martín-Arranz, Laurianne Plastaras, Maria Lia Scribano, Subhasish Sengupta, Nils Teich, My-Linh Tran-Minh, Evanthia Zampeli, Leila Amininejad, Teresa Arroyo, Alain Attar, Ann-Sofie Backman, Anita Bálint, John Beckly, Shomron Ben Horin, Sónia Bernardo, Ludovic Caillo, Bénédicte Caron, María Shanika de Silva, Anna FábiáN, Gionata Fiorino, Ana Gutierrez, Adi Lahat, Mohamed Masmoudi, Marco Mendolaro, Vinciane Muls, Florian Poullenot, Christopher Probert, Catherine Reenaers, Mariann Rutka, Zaman Sarwari, Joanne Sayer, Beatriz Sicilia, Helena Sousa, Catherine van Kemseke, Yamile Zabana, Marco Astegiano, Paul Banim, Dominik Bettenworth, Médina Boualit, Jacob Broder Brodersen, Angeliki Christidou, Rachel Cooney, João Cortez Pinto, Portugal Marília Cravo, Anneline Cremer, Silvio Danese, Antonio di Sabatino, Jan Fallingborg, Antonio Ferronato, Esther Garcia Planella, Sanjay Gupta, Eran Israeli, Samantha Kestenbaum, Lone Larsen, Elisabeth Macken, Nicoletta Mathou, Ágnes Milassin, Joanna Pofelski, Chiara Ricci, Francisco Rodriguez-Moranta, Martin Schmidt-Lauber, Ian Shaw, Marta Soares, Heithem Soliman, Christos Triantos, Konstantinos Zografos, Anurag Agrawal, Alexandre Aubourg, Manuel Barreiro-de Acosta, Jesús Barrio, Daniel Bergemalm, Fernando Bermejo, Giorgia Bodini, Johan Bohr, Dimitrios Christodoulou, Christophe Claessens, Paul Collins, Ruth de Francisco, Santiago Garcia, Sotirios Georgopoulos, Felix Goutorbe, Chrisostomos Kalantzis, Anastasia Kourikou, Vincent Mace, Georgia Malamut, Paula Ministro, Isabelle Nion Larmurier, Elena Ricart, Mélanie Serrero, Juliette Sheridan, Petra Weimers, Vibeke Andersen, Bruno Arroja, Bernd Bokemeyer, Luis Bujanda, Thibault Degand, Carl Eriksson, Cécile Garceau, Henning Glerup, Idan Goren, Lucina Jackson, Stéphane Koch, Francisco Mesonero, Ingrid Ordas, Pauline Riviere, Simone Saibeni, João Soares, Noémie Tavernier, Klaus Theede, Bella Ungar, Elke Bästlein, Antonio Gasbarrini, Andreas Protopapas, Wolfgang Reindl, Fabrizio Bossa, Ailsa Hart, Franz-Josef Heil, Anthony O'Connor, Bas Oldenburg, Luca Pastorelli, null Stephen patchett, Subramaniam Ramakrishnan, John de Caestecker, Ana Echarri, David Kevans, Jürgen Büning, Rosa Coelho, Jeroen Jansen, Benjamin Koslowski, Christopher Wells, Daniel Ceballos, Ingrid König, Hari Padmanabhan, Timi Patani, Raheel Qureshi, Matthieu Allez, Emmanouil Archavlis, Delphine Bonnet, Luisa Guidi, Deirdre Mcnamara, Piero Vernia, Michael Weidenhiller, Lang Alon, Trine Boysen, Charlotte Delattre, Richard Farrell, Rolf-Achim Krüger, Thierry Paupard, Ida Vind, Flavio Caprioli, Vladimir Gancho, Vincent Quentin, Benjamin Avidan, Geert D’Haens, Jane Mccarthy, Jonathon Snook, Konstantinos Soufleris, Frank Zerbib, Dan Carter, Annekatrien Depla, Thomas Eisenbach, Walter Fries, Nikolaos Grammatikos, Saskia Ilegems, Antonio Lopez-Sanroman, Jacques Moreau, Gabriele Riegler, Svend Rietdijk, Marta Rocha, Isabelle Rosa, Barbara Ryan, Yelena Yeremenko, Arnaud Boruchowicz, Filipe Damião, Foteini Laoudi, Andreas Lügering, Giampiero Macarri, Konstantinos Thomopoulos, Luísa Barros, Thomas Blixt, Aurélien Garros, Sam Khorrami, Harry Sokol, Andreas Sturm, Dan Livovsky, Jochen Maul, Heinrich Miks, Vasileios Papadopoulos, Carsten Schmidt, Yifat Snir, Lise Svenningsen, Wafaa Ahmed, Yelena Broitman, Emmanuel Cuillerier, Prashant Kant, Jan Leyden, Lev Lichtenstein, Susana Lopes, Chloé Martineau, Hugh Mulcahy, Axel Schweitzer, Fiona Van Schaik, Hagar Banai, Pauline Danion, Charlotte Dulery, Herma Fidder, Claire Gay, Hervé Hagege, Florence Harnois, Søren Peter Jørgensen, Jens Müller-Ziehm, Michail Oikonomou, Carolina Palmela, Jörg Schulze/Röske, Mark Smith, Tamar Thurm, Francesca Bresso, Hedia Brixi, John Jones, Padraig Macmathuna, Claire Painchart, Yulia Ron, Marianne Vester-Andersen, Gonçalo Alexandrino, Norbert Börner, Mariana Cardoso, Cristina Chagas, Axel Dignaß, Iris Dotan, Charlotte Hedin, Pantelis Karatzas, Panagiotis Kasapidis, Károly Palatka, Georgios Sakizlis, Ana Wilson, Nick Bosanko, Paulo Caldeira, Charlotte Gagniere, Louise Libier, Camille Meunier, Gero Moog, Audrey Pasquion, Roberta Pica, Ayesha Akbar, Nadia Arab, Guillaume Cadiot, João Carvalho, Claire Charpignon, Laus Fellermann, Sigal Fishman, Gerald Fraser, Nathan Gluck, Mark Hoesl, Jarosław Kierkus, Maria Klopocka, Eduardo Martin Arranz, Luis Menchen, Susanna Nikolaus, Anca Petrache, Cyriel Ponsioen, Sabino Riestra, Pilar Robledo, Cristina Rodriguez, Misheal Samer, Matthias Tischer, Joanna Wypych, Julien Baudon, Cristina Bezzio, Gilles Boschetti, Tom Creed, Maria Giulia Demarzo, Stefano Festa, Andrés Figueroa, Mette Julsgaard, Pablo Navarro, Pablo Perez-Galindo, Cléa Rouillon, Emanuele Sablich, Joan Tosca, Mathias Vidon, Marine Vidon, René-Louis Vitte, Anne Wampach, Isabelle Clerc Urmes, Marc Borie, Mathieu Uzzan, Kelly Chatten, Rimmer Peter, Iqbal Tariq, Marta Cossignani, Fiorella Cañete, Tom Holvoet, Susanne Krasz, Sandra Dias, Hadas Abalia, Aziza Abaza, Gal Abramovich, Ingrid Ackzell, Carol Adams, Catherine Addleton, Erika Alfambra, Alicia Algaba, Clare Allcock, Joanna Allison, Karine Amouriaux, Julie Anderson, Emma Anderson, Saskia Appelmans, Lisa Armstrong, Stacey Atkins, Masoumeh Attaran-Bandarabadi, Yvonne Bailey, Stephanie Bardot, Natasha Beck, Lillie Bennett, Jonathan Phil Bergfeld, Ramdane Berkane, Hanne Boey, Louise Bowlas, Joanne Bradley-Potts, Tracy Brear, Nicole Bretlander-Peters, Ellen Brown, Johanna Brown, Elizabeth Buckingham, Katrien Buellens, Rhian Bull, Maura Burke, Leighanne Burns, Julie Burton, Agness Bwalya, Karine Cabanas, Muriel Callaghan, Océane Camou, Debbie Campbell, Elvira Capoferro, Mandy Carnahan, Cornelia Carnio, Anne Carter, Concetta Casali Clack, Leïla Chedouba, Bessie Cipriano, Sophie Claeys, Manon Closset, Dilek Coban, Sara Cococcia, Carolann Coe, Helen Cole, Emilie Collet, Kayleigh Collins, Isabelle Combes, Emma Connor, Kathryn Constantin, Susan Cooke, Nathanaëlle Cornet, Estelle Corrihons, Pilar Corsino, Rosie Cortaville, Donna Cotterill, Amanda Cowton, Harriet Cox, Viktoria Cripps, Amanda Crowder, Tzufit Cukier, Amelia Daniel, Chris Dawe, Jose de Haan, Rosanna de la Croix, Evva Dejonckheere, Juan Delare Villanegro, Guillaume Delaval, Mariangela Delliponti, Aude Delommez, Emilie Detry, Melanie Dhanaratne, Laura Diez Galan, Marie Dodel, Emma Dooks, Joseph Du Cheyron, Linda Duane, Jennifer Dulling Vulgo Cochran, Simona Dyer, Harvey Dymond, Charlotte Ekblad, Kerry Elliott, Ingrid Emmerson, Irène Eugene-Jolchine, Lorna Fleming, Eve Fletcher, Sarah Ford, Greg Forshaw, Angela Foulds, Caroline Francois, Nicole Fuge, Gal Gafni, Miri Ganon, Olga Garcia Nuñez, Laura Garcia Ramirez, Sophie Gelder, Raimonda Gettkowski, Daniela Gilardi, Paolo Giuffrida, Vincent Gobert, Jo Godden, Nuala Godwin, Kay Goulden, Sharon Graham, Charlotte Green, Marie Green, Aboubakar Gueye, Tuba Guler, Ida Gustavsson, Helena Hadjisavvas, Fiona Hammonds, Christina Hantzi, Marion Hauke, Julie Haydock, Orla Hayes, Lizette Helbo Nislev, Jessica Hochstodter, Ashleigh Hogg, Manuela Hölbing, Maureen Holland, Maartje Holsbergen, Linda Howard, Aviya Hoyda, Robert Hull, Jane Irish, Wendy Jackson, Wendy Janssen, Lesley Jeffrey, Sofia Jourdan, Izabela Jutrowska, Chava Kaniel, Theofilos Karezos, Niamh Kelly, Jessica Kelly, Mary Kennedy, Una Kennedy, Joyce Kibaru, Gemma Kirkman, Janine Klaproth, Corinna Kneese, Andrea Koch, Kathleen Kokke, Martha Koppelow, Sabine Krause, Sabine Krauspe, Petra Kwakkenbos, Nunzia Labarile, Hannah Lang, Marianne Lassailly, Martine Leconte, Linda Lepczynski, Emma Levell, Nina Levhar, Kerstin Lindhort, Jessica Lisle, Beatriz Lopez Cauce, Gabriele Lorenz, Ambra Lovati, Tracey Lowry, Margareta Lund, Anne Lutz Vorderbrügge, Suzanne Maansson, Videsheka Madapathage, Maelys Cheviakoff, Alison Magness, Orla Manley, Catherine Manyoni, Ingke Marg, Antonella Marra, Carole Martins, Arianna Massella, Aurore Mathias, Danielle Mervyn, Charlotte Minsart, Sally Mitchell, Kathleen Monks, Mélanie Montero, Alson Moore, Maren Moser, Alison Moss, Angela Mullen, M. Francisca Murciano, Deanna Naylor, Ansgar Nehus, Anne Nicholson, Sarah Nöding, Sinead Nolan, Janet Nörenberg, Clare Northcott, Jim O'Connell, Alison O’Kelly, Noam Orbach-Zingboim, Judit Orobitg, Charlene Otieno, Charlotte Owen, Sarah Patch, Maor Pauker, Renate Pauli, Harriet Pearson, Falgon Peggy, Séverine Petit, Christine Petrissans, Simona Piergallini, Lucy Pippard, Laura Pitt, Gabriella Pócsik, Yoann Poher, Chloé Pomes, Lucy Pritchard, Laura Puchades, Sheena Quaid, Aleem Rana, Dana Raynard, Mykla Reilly, Sonja Reinert, Manuela Reinknecht, Baerbel Renner, Rob Reynolds, Giulia Rizzuto, Matthew Robinson, Joke Robrechts, Eva M. Rodriguez, Efrat Rosenblum, Tamlyn Russel, Ibiyemi Sadare, Noa Salama, Toos Schakel, Anja Schauer, Elisa Schiavoni, Caroline Shaw, Sarah Shelton, Virginie Sicart, Elodie Siouville, Orla Smith, Théo Soude, Sophie Stephenson, Elaine Stephenson, Marjan Steppe, An Sterkx, Jo Stickley, Kathleen Sugrue, Natalia Swietec, Charlotte Tasiaux, Bhavneet Thamu, Susane Thomas, Ogwa Tobi, Kahina Touabi, Shifra Tovi, Julie Tregonning, Laura Turchini, Julia Unkhoff, Olesya Unruh, Nurcan Uzun, Frauke Van Aert, Sandrine Vanden Bergh, Louise Vandenbroucke, Laura Vansteenkiste, Shay Vardit, Valentin Vergriete, Elaine Walker, Eleanor Warner, Olivia Watchorn, Ekaterina Watson, Marie-Claire Wauthier, Belgium Maria Weetman, Margaret Weston, Wiebke West-Petroschka, Susann Wienecke, Kerstin Wierling, Miriam Wiestler, Rebecca Wilcox, Elva Wilhelmsen, Angharad Williams, Georgina Williamson, Deborah Wilson, Kate Wistance, Nicolas Wortmann, Subie Wurie, Karin Yadgar, Gail Young, Megan Young, Julien Aucouturier, Marie- Jo Bertin, Hasnae Bougrine, Marie Coisnon, Antoine Defrance, Kati Gutierrez, Amel Harouz, Laure Jerber, Aida Khlifi, Amina Kirati, Nasaladjine Liworo, Maude Logoltat, Charlotte Mailhat, Chancely M'Bayi, Yasmina Medane, Dalal Merkhoufa, Saouda Mohamed Elhad, Bertille Monthe, Fanny Moyon, Pascaline Rabiega, Jennifer Sekela, Charlotte Thilloy, Naima Hamamouche, Frederic Partisotti, Patrick Blandin, Hocine Mokhtari, Laure Coutard, UCL - SSS/IREC/MONT - Pôle Mont Godinne, UCL - (MGD) Service de gastro-entérologie, Gastroenterology and hepatology, Gastroenterology and Hepatology, and AGEM - Amsterdam Gastroenterology Endocrinology Metabolism
Subjects: Biological Products, Hepatology, Efficacy, Lymphoma, Tumor Necrosis Factor-alpha, Inflammatory Bowel Disease, Gastroenterology, Biologics, Crohn Disease/diagnosis, Inflammatory Bowel Diseases/chemically induced, Colitis, Ulcerative/diagnosis, Cohort Studies, Necrosis, Immunologic Factors/adverse effects, Humans, Female, 03.02. Klinikai orvostan, Prospective Studies, Safety, I-CARE, Cancer, Immunosuppressive Agents
Abstract: BACKGROUND AND AIMS: There is a need to evaluate the benefit-risk ratio of current therapies in inflammatory bowel disease (IBD) patients to provide the best quality of care. The primary objective of I-CARE (IBD Cancer and serious infections in Europe) was to assess prospectively safety concerns in IBD, with specific focus on the risk of cancer/lymphoma and serious infections in patients treated with anti-tumor necrosis factor and other biologic monotherapy as well as in combination with immunomodulators.METHODS: I-CARE was designed as a European prospective longitudinal observational multicenter cohort study to include patients with a diagnosis of Crohn's disease, ulcerative colitis, or IBD unclassified established at least 3 months prior to enrollment.RESULTS: A total of 10,206 patients were enrolled between March 2016 and April 2019, including 6169 (60.4%) patients with Crohn's disease, 3853 (37.8%) with ulcerative colitis, and 184 (1.8%) with a diagnosis of IBD unclassified. Thirty-two percent of patients were receiving azathioprine/thiopurines, 4.6% 6-mercaptopurine, and 3.2% methotrexate at study entry. At inclusion, 47.3% of patients were treated with an anti-tumor necrosis factor agent, 8.8% with vedolizumab, and 3.4% with ustekinumab. Roughly one-quarter of patients (26.8%) underwent prior IBD-related surgery. Sixty-six percent of patients had been previously treated with systemic steroids. Three percent of patients had a medical history of cancer prior to inclusion and 1.1% had a history of colonic, esophageal, or uterine cervix high-grade dysplasia.CONCLUSIONS: I-CARE is an ongoing investigator-initiated observational European prospective cohort study that will provide unique information on the long-term benefits and risks of biological therapies in IBD patients. (EudraCT, Number: 2014-004728-23; ClinicalTrials.gov, Number: NCT02377258).
Published: 2022
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20. Critical care admission following elective surgery was not associated with survival benefit

Author: Kahan, Brennan C., Desponia, Koulenti, Kostoula, Arvaniti, Vanessa, Beavis, Douglas, Campbell, Matthew, Chan, Rui, Moreno, Pearse, Rupert M., Scott, Beattie, Pierre-Alain, Clavien, Nicolas, Demartines, Lee, A Fleisher, Mike, Grocott, James, Haddow, Andreas, Hoeft, Peter, Holt, Naomi, Pritchard, Andrew, Rhodes, Duminda, Wijeysundera, Matt, Wilson, Tahania, Ahmed, Kirsty, Everingham, Russell, Hewson, Marta, Januszewska, Rupert, M Pearse, Mandeep-Kaur, Phull, Richard, Halliwell, Mark, Shulman, Paul, Myles, Werner, Schmid, Michael, Hiesmayr, Patrick, Wouters, Stefan de Hert, Suzana, Lobo, Xiangming, Fang, Lars, Rasmussen, Emmanuel, Futier, Matthieu, Biais, Aurélien, Venara, Karem, Slim, Michael, Sander, Despoina, Koulenti, Mathew, Chan, Atul, Kulkarni, Susilo, Chandra, Aida, Tantri, Emad, Geddoa, Muntadhar, Abbas, Giorgio Della Rocca, Datin, Sivasakthi, Marzida, Mansor, Pastor, Luna, Arthur, Bouwman, Wolfgang, Buhre, Tim, Short, Tunde, Osinaike, Ricardo, Matos, Ioana, Grigoras, Mikhail, Kirov, Denis, Protsenko, Bruce, Biccard, Cesar, Aldecoa, Michelle, Chew, Christoph, Hofer, Martin, Hubner, James, Ditai, Tamas, Szakmany, Lee, Fleisher, Marissa, Ferguson, Michael, Macmahon, Ritchie, Cherian, Helen, Currow, Kathirgamanathan, Kanathiban, David, Gillespie, Edward, Pathmanathan, Katherine, Phillips, Jenifer, Reynolds, Joanne, Rowley, Jeanene, Douglas, Ross, Kerridge, Sameer, Garg, Michael, Bennett, Megha, Jain, David, Alcock, Nico, Terblanche, Rochelle, Cotter, Kate, Leslie, Marcelle, Stewart, Nicolette, Zingerle, Antony, Clyde, Oliver, Hambidge, Adam, Rehak, Sharon, Cotterell, Wilson Binh Quan Huynh, Timothy, Mcculloch, Erez, Ben-Menachem, Thomas, Egan, Jennifer, Cope, Paul, Fellinger, Simone, Haselberger, Caroline, Holaubek, Paul, Lichtenegger, Florian, Scherz, Franz, Hoffer, Veronika, Cakova, Andreas, Eichwalder, Norbert, Fischbach, Reinhold, Klug, Elisabeth, Schneider, Martin, Vesely, Reinhart, Wickenhauser, Karl Gernot Grubmueller, Marion, Leitgeb, Friedrich, Lang, Nancy, Toro, Marlene, Bauer, Friedrich, Laengle, Thomas, Mayrhofer, Christian, Buerkle, Karin, Forstner, Reinhard, Germann, Harald, Rinoesl, Elke, Schindler, Ernst, Trampitsch, Gerhard, Fritsch, Christian, Szabo, Jawad, Bidgoli, Hans, Verdoodt, Patrice, Forget, David, Kahn, Fernande, Lois, Mona, Momeni, Caroline, Prégardien, Audrey, Pospiech, Arnaud, Steyaert, Laurent, Veevaete, Dirk De Kegel, Karen De Jongh, Luc, Foubert, Carine, Smitz, Marcel, Vercauteren, Jan, Poelaert, Veerle Van Mossevelde, Jacques, Abeloos, Stefaan, Bouchez, Marc, Coppens, Luc De Baerdemaeker, Isabel, Deblaere, Ann De Bruyne, Stefan De Hert, Kristine, Fonck, Bjorn, Heyse, Tom, Jacobs, Koen, Lapage, Anneliese, Moerman, Martine, Neckebroek, Aliaksandra, Parashchanka, Nathalie, Roels, Nancy Van Den Eynde, Michael, Vandenheuvel, Jurgen Van Limmen, Ann, Vanluchene, Caroline, Vanpeteghem, Piet, Wyffels, Christel, Huygens, Punitha, Vandenbempt, Marc Van de Velde, Dimitri, Dylst, Bruno, Janssen, Evelien, Schreurs, Fábia Berganton Aleixo, Keulle, Candido, Hugo Dias Batista, Mario, Guimarães, Jaqueline, Guizeline, João, Hoffmann, Suzana, M Lobo, Francisco Ricardo Lobo, Vinícius, Nascimento, Katia, Nishiyama, Lucas, Pazetto, Daniela, Souza, Rodrigo Souza Rodrigues, Ana Maria Vilela Dos Santos, Jaquelline, Jardim, Joao, Silva, Paulo do Nascimento Junior, Thalissa Hermínia Baio, Gabriel Isaac Pereira de Castro, Henri Roger Watanabe Oliveira, Cristina Prata Amendola, Gutemberg, Cardoso, Daniela, Ortega, Ana Flavia Brotto, Mirella Cristine De Oliveira, Álvaro, Réa-Neto, Fernando, Dias, Pedro, Azambuja, Marcos Freitas Knibel, Antonio, Martins, William, Almeida, Calim Neder Neto, Maria Angela Tardelli, Eliana, Caser, Marcio, Machado, Crisitiano, Aguzzoli, Sérgio, Baldisserotto, Fernanda Beck Tabajara, Fernanda, Bettega, La Hore Correa Rodrigues Júnior, Julia de Gasperi, Lais, Faina, Marcos Farias Nolasco, Bruna Ferreira da Costa Fischer, Mariana Fosch de Campos Ferreira, Cristina, Hartmann, Marta, Kliemann, Gustavo Luis Hubert Ribeiro, Julia Merladete Fraga, Thiago Motta Netto, Laura Valduga Pozza, Paulo Rafael Wendling, Caroline, Azevedo, Juliana, Garcia, Marcel, Lopes, Bernardo, Maia, Paula, Maselli, Ralph, Melo, Weslley, Mendes, Matheus, Neves, Jacqueline, Ney, Claudio, Piras, Christopher, Applewhaite, Adrienne, Carr, Lorraine, Chow, Kaylene, Duttchen, Julena, Foglia, Michael, Greene, Ashley, Hinther, Kendra, Houston, Thomas Jared McCormick, Jennifer, Mikhayel, Sam, Montasser, Alex, Ragan, Andrew, Suen, Adrianna, Woolsey, Hai Chuan Yu, Duane, Funk, Stephen, Kowalski, Regina, Legaspi, Heather, Mcdonald, Faisal, Siddiqui, Jeremy, Pridham, Bernadette, Rowe, Sonia, Sampson, Barton, Thiessen, Geoff, Zbitnew, Andre, Bernard, Ronald, George, Philip, Jones, Rita, Moor, Naveed, Siddiqui, Alexandra, Wolfer, Diem, Tran, Denyse, Winch, Gary, Dobson, Thomas, Mccormick, Osama, Montasser, Richard, Hall, Leyla, Baghirzada, Si Yuan Dai, Gregory, Hare, Esther, Lee, Uma, Shastri, Albert, Tsui, Anmol, Yagnik, Danielle, Alvares, Stephen, Choi, Heather, Dwyer, Kathrina, Flores, Colin, Mccartney, Priya, Somascanthan, Carroll, Jo, Janneth, Pazmino-Canizares, Noam, Ami, Vincent, Chan, Anahi, Perlas, Ruth, Argue, Katie, Lavis, Kelly, Mayson, Ying, Cao, Hong, Gao, Tingju, Hu, Jie, Lv, Jian, Yang, Yang, Yang, Zhong, Yi, Jing, Zhou, Xiaohua, Zou, Miao, He, Xiaoying, Li, Dihuan, Luo, Haiying, Wang, Tian, Yu, Liyong, Chen, Lijun, Wang, Yunfei, Cai, Zhongming, Cao, Yanling, Li, Jiaxin, Lian, Haiyun, Sun, Sheng, Wang, Zhipeng, Wang, Kenru, Wang, Zhu, Yi, Xindan, Du, Hao, Fan, Yunbin, Fu, Lixia, Huang, Yanming, Huang, Haifang, Hwan, Hong, Luo, Pi-Sheng, Qu, Fan, Tao, Zhen, Wang, Guoxiang, Wang, Shun, Wang, Yan, Zhang, Xiaolin, Zhang, Chao, Chen, Weixing, Wang, Zhengyuan, Liu, Lihua, Fan, Jing, Tang, Yijun, Chen, Yongjie, Chen, Yangyang, Han, Changshun, Huang, Guojin, Liang, Jing, Shen, Jun, Wang, Qiuhong, Yang, Jungang, Zhen, Haidong, Zhou, Junping, Chen, Zhang, Chen, Xiaoyu, Li, Meng, Bo, Haiwang, Ye, Xiaoyan, Zhang, Yanbing, Bi, Jianqiao, Cao, Fengying, Guo, Hong, Lin, Yang, Liu, Meng, Lv, Pengcai, Shi, Xiumei, Song, Chuanyu, Sun, Yongtao, Sun, Yuelan, Wang, Shenhui, Wang, Min, Zhang, Rong, Chen, Jiabao, Hou, Yan, Leng, Qing-Tao, Meng, Qian, Li, Zi-Ying, Shen, Zhong-Yuan, Xia, Rui, Xue, Yuan, Zhang, Zhao, Bo, Xian-Jin, Zhou, Qiang, Chen, Huinan, Guo, Yongqing, Guo, Yuehong, Qi, Zhi, Wang, Jianfeng, Wei, Weiwei, Zhang, Lina, Zheng, Bao, Qi, Yaqiu, Chen, Yijiao, Chen, Yue, Fei, Nianqiang, Hu, Xuming, Hu, Min, Lei, Xiaoqin, Li, Xiaocui, Lv, Fangfang, Miao, Lingling, Ouyang, Qian, Lu, Conyu, Shen, Sun, Yu, Yuting, Wang, Dong, Wang, Chao, Wu, Liyuan, Xu, Jiaqi, Yuan, Lina, Zhang, Huan, Zhang, Yapping, Zhang, Jinning, Zhao, Chong, Zhao, Lei, Zhao, Tianzhao, Zheng, Dachun, Zhou, Haiyan, Zhou, Zhou, Ce, Kaizhi, Lu, Ting, Zhao, Changlin, He, Hong, Chen, Shasha, Chen, Baoli, Cheng, Jie, He, Lin, Jin, Caixia, Li, Hui, Li, Yuanming, Pan, Yugang, Shi, Xiao Hong Wen, Shuijing, Wu, Guohao, Xie, Kai, Zhang, Bing, Zhao, Xianfu, Lu, Feifei, Chen, Qisheng, Liang, Xuewu, Lin, Yunzhi, Ling, Gang, Liu, Jing, Tao, Yang, Lu, Jialong, Zhou, Fumei, Chen, Yunlin, Feng, Benchao, Hou, Jiamei, Lin, Mei, Liu, Foquan, Luo, Xiaoyun, Shi, Yingfen, Xiong, Lin, Xu, Shuangjia, Yang, Qin, Zhang, Huaigen, Zhang, Weihong, Zhao, Weilu, Zhao, Yun, Bai, Linbi, Chen, Sijia, Chen, Qinxue, Dai, Wujun, Geng, Kunyuan, Han, Xin, He, Luping, Huang, Binbin, Ji, Danyun, Jia, Shenhui, Jin, Qianjun, Li, Dongdong, Liang, Shan, Luo, Lulu, Lwang, Yunchang, Mo, Yuanyuan, Pan, Xinyu, Qi, Meizi, Qian, Jinling, Qin, Yelong, Ren, Yiyi, Shi, Junlu, Wang, Junkai, Wang, Leilei, Wang, Junjie, Xie, Yixiu, Yan, Yurui, Yao, Mingxiao, Zhang, Jiashi, Zhao, Xiuxiu, Zhuang, Yanqiu, Ai, Fang, Du, Long, He, Ledan, Huang, Zhisong, Li, Huijuan, Li, Yetong, Li, Liwei, Li, Meng, Su, Yazhuo, Yuan, Enman, Zhang, Jie, Zhang, Shuna, Zhao, Zhenrong, Ji, Ling, Pei, Wang, Li, Chen, Chen, Beibei, Dong, Jing, Li, Ziqiang, Miao, Hongying, Mu, Chao, Qin, Lin, Su, Zhiting, Wen, Keliang, Xie, Yonghao, Yu, Fang, Yuan, Xianwen, Hu, Zhang, Ye, Wangpin, Xiao, Zhipeng, Zhu, Qingqing, Dai, Kaiwen, Fu, Rong, Hu, Xiaolan, Hu, Song, Huang, Yaqi, Li, Yingping, Liang, Shuchun, Yu, Zheng, Guo, Yan, Jing, Tang, Na, Jie, Wu, Dajiang, Yuan, Ruilin, Zhang, Xiaoying, Zhao, Yuhong, Li, Hui-Ping, Bai, Chun-Xiao, Liu, Fei-Fei, Liu, Wei, Ren, Xiu-Li, Wang, Guan-Jie, Xu, Na, Hu, Bo, Li, Yangwen, Ou, Yongzhong, Tang, Shanglong, Yao, Shihai, Zhang, Cui-Cui, Kong, Bei, Liu, Tianlong, Wang, Wei, Xiao, Bo, Lu, Yanfei, Xia, Jiali, Zhou, Fang, Cai, Pushan, Chen, Shuangfei, Hu, Hongfa, Wang, Qiong, Xu, Liu, Hu, Liang, Jing, Bin, Li, Qiang, Liu, Yuejiang, Liu, Xinjian, Lu, Zhen Dan Peng, Xiaodong, Qiu, Quan, Ren, Youliang, Tong, Jin, Wang, Yazhou, Wen, Qiong, Wu, Jiangyan, Xia, Jue, Xie, Xiapei, Xiong, Shixia, Xu, Tianqin, Yang, Hui, Ye, Ning, Yin, Jing, Yuan, Qiuting, Zeng, Baoling, Zhang, Kang, Zheng, Jing, Cang, Shiyu, Chen, Fan, Yu, Shuying, Fu, Xiaodong, Ge, Baolei, Guo, Wenhui, Huang, Linghui, Jiang, Xinmei, Jiang, Liu, Yi, Yan, Pan, Yun, Ren, Shan, Qi, Jiaxing, Wang, Fei, Wang, Chi, Wu, Xiaoguang, Zhang, Ida Cecilie Christiansen, Simon Nørgaard Granum, Bodil Steen Rasmussen, Morten, Daugaard, Rajiv, Gambhir, Guðný Erla Steingrímsdóttir, Peter, Jensen-Gadegaard, Karsten Skovgaard Olsen, Hanna, Siegel, Katrine Zwicky Eskildsen, Mona Ring Gätke, Ida, Wibrandt, Simon Bisgaard Heintzelmann, Kai Henrik Wiborg Lange, Rune Sarauw Lundsgaard, Louise, Amstrup-Hansen, Claus, Hovendal, Michael, Larsen, Mette, Lenstrup, Tina, Kobborg, Jens Rolighed Larsen, Anette Barbre Pedersen, Søren Hübertz Smith, Rebecca Monett Oestervig, Arash, Afshari, Cheme, Andersen, Kim, Ekelund, Erik Lilja Secher, Birgitte, Brandsborg, Helene, Beloeil, Sigismond, Lasocki, Alexandre, Ouattara, Marlene, Sineus, Serge, Molliex, Marie Lim Legouge, Florent, Wallet, Antoine, Tesniere, Christophe, Gaudin, Paul, Lehur, Emma, Forsans, Stéphane de Rudnicki, Valerie Serra Maudet, Didier, Mutter, Ghassan, Sojod, Mehdi, Ouaissi, Jean-Marc, Regimbeau, Jacques, Desbordes, Nicolas, Comptaer, Diae El Manser, Sabine, Ethgen, Gilles, Lebuffe, Patrick, Auer, Christine, Härtl, Maria, Deja, Kirill, Legashov, Susanne, Sonnemann, Carola, Wiegand-Loehnert, Elke, Falk, Marit, Habicher, Stefan, Angermair, Beatrix, Laetsch, Katrin, Schmidt, Christian Von Heymann, Axel, Ramminger, Florian, Jelschen, Svenja, Pabel, Andreas, Weyland, Elke, Czeslick, Jochen, Gille, Michael, Malcharek, Armin, Sablotzki, Katharina, Lueke, Peter, Wetzel, Joerg, Weimann, Franz-Peter, Lenhart, Florian, Reichle, Frederike, Schirmer, Michael, Hüppe, Karl, Klotz, Carla, Nau, Julika, Schön, Thomas, Mencke, Christina, Wasmund, Carla, Bankewitz, Georg, Baumgarten, Andreas, Fleischer, Vera, Guttenthaler, Yvonne, Hack, Katharina, Kirchgaessner, Olja, Männer, Marlen, Schurig-Urbaniak, Rafael, Struck, Rebekka van Zyl, Maria, Wittmann, Ulrich, Goebel, Sarah, Harris, Siegfried, Veit, Evangelia, Andreadaki, Flora, Souri, Ioannis, Katsiadramis, Anthi, Skoufi, Maria, Vasileiou, Eleni, Aimoniotou-Georgiou, Anastasios, Katsourakis, Fotini, Veroniki, Glyceria, Vlachogianni, Konstantina, Petra, Dimitra, Chlorou, Eirini, Oloktsidou, Vasileios, Ourailoglou, Konstantinos, Papapostolou, Georgia, Tsaousi, Panagoula, Daikou, Georgia, Dedemadi, Ioannis, Kalaitzopoulos, Christos, Loumpias, Sotirios, Bristogiannis, Nikolaos, Dafnios, Georgios, Gkiokas, Elissaios, Kontis, Dimitra, Kozompoli, Aspasia, Papailia, Theodosios, Theodosopoulos, Christol, Bizios, Anastasia, Koutsikou, Aleaxandra, Moustaka, Ioannis, Plaitakis, Apostolos, Armaganidis, Theodora, Christodoulopoulou, Mihail, Lignos, Maria, Theodorakopoulou, Andreas, Asimakos, Eleni, Ischaki, Angeliki, Tsagkaraki, Spyros, Zakynthinos, Eleni, Antoniadou, Ioannis, Koutelidakis, Dimitrios, Lathyris, Irene, Pozidou, Nikolaos, Voloudakis, Maria, Dalamagka, Elena, Gkonezou, Christos, Chronis, Dimitra, Manolakaki, Dimitris, Mosxogiannidis, Tatiana, Slepova, Isaia-Sissy, Tsakiridou, Claire Lampiri Lampiri, Anastasia Vachlioti Vachlioti, Christos Panagiotakis Panagiotakis, Dimitrios Sfyras Sfyras, Fotios Tsimpoukas Tsimpoukas, Athanasia, Tsirogianni, Elena, Axioti, Andreas, Filippopoulos, Elli, Kalliafa, George, Kassavetis, Petros, Katralis, Ioannis, Komnos, Georgios, Pilichos, Ifigenia, Ravani, Antonis, Totis, Eymorfia, Apagaki, Andromachi, Efthymiadi, Nikolaos, Kampagiannis, Theoniki, Paraforou, Agoritsa, Tsioka, Georgios, Georgiou, Aristeidis, Vakalos, Aggeliki, Bairaktari, Efthimios, Charitos, George, Markou, Panagiota, Niforopoulou, Nikolaos, Papakonstantinou, Evdoxia, Tsigou, Archontoula, Xifara, Menelaos, Zoulamoglou, Panagiota, Gkioni, Stylianos, Karatzas, Aikaterini, Kyparissi, Efstratios, Mainas, Ioannis, Papapanagiotou, Theonymfi, Papavasilopoulou, George, Fragandreas, Eleni, Georgopoulou, Eleni, Katsika, Kyriakos, Psarras, Eirini, Synekidou, Maria, Verroiotou, Evangelia, Vetsiou, Donika, Zaimi, Athina, Anagnou, Konstantinos, Apostolou, Theodora, Melissopoulou, Theophilos, Rozenberg, Christos, Tsigris, Georgios, Boutsikos, Vasileios, Kalles, Nikolaos, Kotsalas, Christina, Lavdaiou, Fotini, Paikou, Georgia-Laura, Panagou, Anna, Spring, Ioannis, Botis, Maria, Drimala, Georgios, Georgakakis, Ellada, Kiourtzieva, Panagiota, Ntouma, Apostolos, Prionas, Kyriakos, Xouplidis, Eleftheria, Dalampini, Chrysavgi, Giannaki, Christina, Iasonidou, Orestis, Ioannidis, Athina, Lavrentieva, Athena, Lavrentieva, George, Papageorgiou, Maria, Kokkinoy, Maria, Stafylaraki, Stylianos, Gaitanakis, Periclis, Karydakis, Josef, Paltoglou, Panagiotis, Ponireas, Panagiotis, Chaloulis, Athanasios, Provatidis, Anisoglou, Sousana, Varvara Vanessa Gardikou, Maria, Konstantivelli, Olga, Lataniotou, Elisavet, Lisari, Maria, Margaroni, Konstantinos, Stamatiou, Edouardos, Nikolaidis, Ioannis, Pnevmatikos, Eleni, Sertaridou, Alexandros, Andreou, Eleni, Arkalaki, Elias, Athanasakis, Fotini, Chaniotaki, Aikaterini, Chatzimichali, Maria, Christofaki, Despina, Dermitzaki, Klara, Fiorentza, Georgios, Frantzeskos, Elisavet, Geromarkaki, Kalliopi, Kafkalaki, Marina, Kalogridaki, Konstyllia, Karydi, Sofia, Kokkini, Georgios, Kougentakis, Tatiana, Lefaki, Emmanouhl, Lilitsis, Aikaterini, Makatounaki, Polychronis, Malliotakis, Dimosthenis, Michelakis, Maria, Neonaki, Vasileia, Nyktari, Iliana, Palikyra, Eleftherios, Papadakis, Alexandra, Papaioannou, Konstantinos, Sfakianakis, Maria, Sgouraki, Xenia, Souvatzis, Anastasia, Spartinou, Nefeli, Stefanidou, Paulina, Syrogianni, Georgia, Tsagkaraki, Elena, Arnaoutoglou, Christina, Arnaoutoglou, Christina, Bali, Vasilios, Bouris, Rodamanthos, Doumos, Konstantia-Paraskevi, Gkini, Clio, Kapaktsi, Vasilios, Koulouras, Arian, Lena, Dimitra, Lepida, Evangelos, Michos, Dimitrios, Papadopoulos, Minas, Paschopoulos, Vaia Aliki Rompou, Ioanna, Siouti, Stavros, Tsampalas, Ourania, Ververidou, Georgios, Zilis, Alexandra, Charlalampidoy, Gregory, Christodoulidis, Andreas, Flossos, Konstantinos, Stamoulis, Man Shing Caleb Tsang, Man Shing Tsang, Man Ling Lai, Chi Pang Yip, Hey Man Heymans Chan, Bassanio, Law, Wing Sze Li, Hiu Man Chu, Emily Gar Yee Koo, Chi Cheong Joe Lam, Ka Ho Cheng, Tracy, Lam, Susanna, Chu, Wing Yan Lam, Kin Wai Kevin Wong, Dilys, Kwok, Ching Yue Janice Hung, Wai Kit Jacky Chan, Wing, Lamwong, Chun Kwong Eric Chung, Shu Kai Ma, Shuchi, Kaushik, Bhagyesh, Shah, Dhiren, Shah, Sanjay, Shah, Praburaj, Ar, Radhakrishnan, Muthuchellappan, Vandana, Agarwal, Jigeeshu, Divatia, Sanghamitra, Mishra, Ganesh, Nimje, Swati, Pande, Sukhada, Savarkar, Aditi, Shrivastava, Martin, Thomas, Shashikant, Yegnaram, Rahmat, Hidayatullah, Nasman, Puar, Sumara, Niman, Imai, Indra, Zulkarnain, Hamzah, Annika, Yuliana, Ucu Nurhadiat Abidin, Ade Nurkacan Dursin, Andri, Kurnia, Ade, Susanti, Dini, Handayani, Mahaalit Alit Aribawa, Aryabiantara, Arya, Tjokorda Gde Agung Senapathi, Utara Hartawan Utara, Widnyana Made Wid, Semarawima, Wima, Wiryana Made Wir, Brillyan, Jehosua, Jonathan, Kaunang, Eka Yudha Lantang, Rini, Najoan, Neil, Waworuntu, Hadi, Awad, Akram, Fuad, Burair, Geddoa, Abdel Razzaq Khalaf, Sabah Al Hussaini, Safauldeensalem, Albaj, Maithem, Kenber, Alessandra, Bettinelli, Savino, Spadaro, Carlo Alberto Volta, Luigi, Giancarlo, Vicari, Sottosanti, Lorenzo, Spagnesi, Ilaria, Toretti, Chiara, Alloj, Silvano, Cardellino, Livio, Carmino, Eleonora, Costanzo, Lucia Caterina Fanfani, Maria Teresa Novelli, Agostino, Roasio, Mattia, Bellandi, Luigi, Beretta, Elena, Bignami, Speranza, Bocchino, Luca, Cabrini, Daniele, Corti, Giovanni, Landoni, Roberta, Meroni, Elena, Moizo, Giacomo, Monti, Margherita, Pintaudi, Valentina Paola Plumari, Daiana, Taddeo, Valentina, Testa, Dario, Winterton, Alberto, Zangrillo, Luigi Maria Cloro, Chiara, Colangelo, Antonio, Colangelo, Giuseppe, Rotunno, Miguel Paludi Angel, Cloro Paolo Maria, Antonio, Pata, Vieri, Parrini, Alessandro, Gatta, Mauro, Nastasi, Carla, Tinti, Mario, Arrigo, Angelo, Benevento, Corrado, Bottini, Maurizio, Cannavo', Christian, Gastaldi, Alessandro, Marchesi, Angelantonio, Pascazio, Pata, Francesco, Emilio, Pozzi, Alberto, Premoli, Gaetano, Tessera, Luca, Boschi, Rocco, D'Andrea, Federico, Ghignone, Gilberto, Poggioli, Andrea, Sibilio, Mario, Taffurelli, Giampaolo, Ugolini, Mohd Azuan Ab Majid, Rusnah Ab Rahman, James, Joseph, Furquan, Pathan, Mohammad Hafizshah Sybil Shah, Huey Ling Yap, Seleen, Cheah, Im Im Chin, Ji Keon Looi, Siew Ching Tan, Sheshendrasurian, Visvalingam, Fan Yin Kwok, Chew Kiok Lee, Tse Siang Tan, Sze Meng Wong, Noor Hairiza Abdullah, Chiat Fong Liew, Lovenia, Luxuman, Nor Hafizah Mohd Zin, Muhamad Faiz Norddin, Raja Liza Raja Alias, Juan Yong Wong, Johnny, Yong, Mohd Tarmimi Bin Mustapha, Weng Ken Chan, Norizawati, Dzulkipli, Pei Xuan Kuan, Yew Ching Lee, Anita, Alias, Eng Ching Guok, Chiun Chen Jee, Brian Rhadamantyne Ramon, Cheng Wong Weng, Fara Nur Idayu Abd Ghafar, Faizal Zuhri Aziz, Nabilah, Hussain, Hooi Sean Lee, Ismawaty, Sukawi, Yuan Liang Woon, Husni Zaeem Abd Hadi, Ummi Azmira Ahmad Azam, Abdul Hafiz Alias, Saiful Aizar Kesut, Jun May Lee, Dar Vin Ooi, Hetty Ayuni Sulaiman, Tengku Alini Tengku Lih, Jeyaganesh, Veerakumaran, Eder, Rojas, Gerardo Esteban Alvarez Resendiz, Darcy Danitza Mari Zapata, Julio Cesar Jesús Aguilar López, Armando Adolfo Alvarez Flores, Juan Carlosc Bravo Amador, Erendira Jocelin Dominguez Avila, Laura Patricia González Aquino, Ricardo Lopez Rodriguez, Mariana Torres Landa, Emma, Urias, Markus, Hollmann, Abraham, Hulst, Osne, Kirzner, Benedikt, Preckel, Ankie Koopman-van Gemert, Marc, Buise, Noortje, Tolenaar, Eric, Weber, Jennifer de Fretes, Peter, Houweling, Patricia, Ormskerk, Jasper Van Bommel, Marcus, Lance, Valerie, Smit-Fun, Tom van Zundert, Peter, Baas, Hans Donald de Boer, Joost, Sprakel, Renske, Elferink-Vonk, Peter, Noordzij, Laura van Zeggeren, Bastiaan, Brand, Rob, Spanjersberg, Janneke Ten Bokkel-Andela, Janneke, Numan, Wilton van Klei, Bas van Zaane, Christa, Boer, Yoni van Duivenvoorde, Jens Peter Hering, Harry, Zonneveldt, Doug, Campbell, Siobhan, Hoare, Sahayam, Santa, Sara Jane Allen, Rachel, Bell, Hyun-Min David Choi, Matthew, Drake, Helen, Farrell, Kushlin, Higgie, Kerry, Holmes, Nicole, Jenkins, Chang Joon Kim, Steven, Kim, Kiew Chai Law, Davina, Mcallister, Karen, Park, Karen, Pedersen, Leesa, Pfeifer, Timothy, Salmond, Martin, Steynor, Michael, Tan, Ellen, Waymouth, Ahmad Sufian Ab Rahman, John, Armstrong, Rosie, Dudson, Nia, Jenkins, Jayashree, Nilakant, Seigne, Richard, Pardeep, Virdi, Liane, Dixon, Roana, Donohue, Mehreen, Farrow, Ross, Kennedy, Henderson, Marissa, Margie, Mckellow, Delany, Nicola, Rebecca, Pascoe, Stephen John Roberts, George, Rowell, Matthew, Sumner, Paul, Templer, Shardha, Chandrasekharan, Graham, Fulton, Jammer, Ib, Marlynn, Ali, Richard, More, Leona, Wilson, Yuan Hsuan Chang, Julia, Chang, Carolyn, Fowler, Jonathan, Panckhurst, Rachel, Sara, Francois, Stapelberg, Veronica, Cherrett, Donna Louise Ganter, Lloyd, Mccann, 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Bhavika, Daya, Leanne, Drummond, Ali, Elabib, Ehab Helmy Abdel Goad, Ismail, E Goga, Riaz, Goga, Harrichandparsad, R, Richard, E Hodgson, Jordaan, J, Nicky, Kalafatis, Christian, Kampik, T Landers, A, Emil, Loots, Rajhmum, Madansein, Anil, Madaree, Thandinkosi, E Madiba, Vukani, T Manzini, Mbali, Mbuyisa, Rajan, Moodley, Mduduzi, Msomi, Innocent, Mukama, Desigan, Naidoo, Rubeshan, Naidoo, Tesuven, K Naidu, Sindiswa, Ntloko, Eneshia, Padayachee, Lucelle, Padayachee, Martijn, Phaff, Bala, Pillay, Desigan, Pillay, Lutchmee, Pillay, Anupa, Ramnarain, Suren, R Ramphal, Paul, Ryan, Ahmed, Saloojee, Motshedisi, Sebitloane, Noluyolo, Sigcu, Jenna, L Taylor, Alexandra, Torborg, Linda, Visser, Philip, Anderson, Alae, Conradie, Mathew de Swardt, Martin de Villiers, Johan, Eikman, Riaan, Liebenberg, Johan, Mouton, Abbey, Paton, Louwrence van der Merwe, Candice, Wilscott-Davids, Wendy Joan Barrett, Marlet, Bester, Johan de Beer, Jacques, Geldenhuys, Hanni, Gouws, Jan-Hendrik, Potgieter, Magdel, Strydom, Edwin, Wilberforce-Turton, Rubendraj, R Chetty, Subash, Chirkut, Larissa, Cronje, Kim de Vasconcellos, Nokukhanya, Z Dube, N Sibusiso Gama, Garyth, M Green, Randolph, Green-Thompson, Suman Mewa Kinoo, Prenolin, Kistnasami, Kapil, Maharaj, Manogaran, S Moodley, Sibongile, J Mothae, Ruvashni, Naidoo, Aslam, M, Noorbhai, F, Vivesh, Rughubar, Jenendhiran, Reddy, Avesh, Singh, David, L Skinner, Murray, J Smith, Bhagwan, Singh, Ravi, Misra, Maheshwar, Naidoo, Pireshin, Ramdharee, Yvonne, Selibea, Selina, Sewpersad, Shailendra, Sham, Joseph, D Wessels, Cucu, Africander, Tarek, Bejia, Stephen, P Blakemore, Marisa, Botes, Bimalshakth, Bunwarie, Carlos, B Hernandez, Mohammud, A Jeeraz, Dagmara, A Legutko, Acela, G Lopez, Jenine, N De Meyer, Tanaka, Muzenda, Noel, Naidoo, Maryam, Patel, Rao, Pentela, Marina, Junge, Naj, Mansoor, Lana, Rademan, Pawel, Scislowski, Ismail, Seedat, Bianca van den Berg, Doreen van der Merwe, Steyn van Wyk, Komalan, Govender, Darshan, Naicker, Rajesh, Ramjee, 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Tsang, Man Shing, Lai, Man Ling, Yip, Chi Pang, Chan, Hey Man Heyman, Law, Bassanio, Li, Wing Sze, Chu, Hiu Man, Koo, Emily Gar Yee, Lam, Chi Cheong Joe, Cheng, Ka Ho, Lam, Tracy, Chu, Susanna, Lam, Wing Yan, Wong, Kin Wai Kevin, Kwok, Dily, Hung, Ching Yue Janice, Chan, Wai Kit Jacky, LamWong, Wing, Chung, Chun Kwong Eric, Ma, Shu Kai, Kaushik, Shuchi, Shah, Bhagyesh, Shah, Dhiren, Shah, Sanjay, Ar, Praburaj, Muthuchellappan, Radhakrishnan, Agarwal, Vandana, Divatia, Jigeeshu, Mishra, Sanghamitra, Nimje, Ganesh, Pande, Swati, Savarkar, Sukhada, Shrivastava, Aditi, Thomas, Martin, Yegnaram, Shashikant, Hidayatullah, Rahmat, Puar, Nasman, Niman, Sumara, Indra, Imai, Hamzah, Zulkarnain, Yuliana, Annika, Abidin, Ucu Nurhadiat, Dursin, Ade Nurkacan, Kurnia, Andri, Susanti, Ade, Handayani, Dini, Aribawa, Mahaalit Alit, Arya, Aryabiantara, Senapathi, Tjokorda Gde Agung, Utara, Utara Hartawan, Wid, Widnyana Made, Wima, Semarawima, Wir, Wiryana Made, Jehosua, Brillyan, Kaunang, Jonathan, Lantang, Eka Yudha, Najoan, Rini, Waworuntu, Neil, Awad, Hadi, Fuad, Akram, Geddoa, Burair, Khalaf, Abdel Razzaq, Al hussaini, Sabah, Albaj, Safauldeensalem, Kenber, Maithem, Bettinelli, Alessandra, Spadaro, Savino, Volta, Carlo Alberto, Giancarlo, Luigi, Sottosanti, Vicari, Spagnesi, Lorenzo, Toretti, Ilaria, Alloj, Chiara, Cardellino, Silvano, Carmino, Livio, Costanzo, Eleonora, Fanfani, Lucia Caterina, Novelli, Maria Teresa, Roasio, Agostino, Bellandi, Mattia, Beretta, Luigi, Bignami, Elena, Bocchino, Speranza, Cabrini, Luca, Corti, Daniele, Landoni, Giovanni, Meroni, Roberta, Moizo, Elena, Monti, Giacomo, Pintaudi, Margherita, Plumari, Valentina Paola, Taddeo, Daiana, Testa, Valentina, Winterton, Dario, Zangrillo, Alberto, Cloro, Luigi Maria, Colangelo, Chiara, Colangelo, Antonio, Rotunno, Giuseppe, Angel, Miguel Paludi, Maria, Cloro Paolo, Pata, Antonio, Parrini, Vieri, Gatta, Alessandro, Nastasi, Mauro, Tinti, Carla, Arrigo, Mario, Benevento, Angelo, Bottini, Corrado, Cannavo’, Maurizio, Gastaldi, Christian, Marchesi, Alessandro, Pascazio, Angelantonio, Pata, Francesco, Pozzi, Emilio, Premoli, Alberto, Tessera, Gaetano, Boschi, Luca, D’Andrea, Rocco, Ghignone, Federico, Poggioli, Gilberto, Sibilio, Andrea, Taffurelli, Mario, Ugolini, Giampaolo, Ab Majid, Mohd Azuan, Ab Rahman, Rusnah, Joseph, Jame, Pathan, Furquan, Shah, Mohammad Hafizshah Sybil, Yap, Huey Ling, Cheah, Seleen, Chin, Im Im, Looi, Ji Keon, Tan, Siew Ching, Visvalingam, Sheshendrasurian, Kwok, Fan Yin, Lee, Chew Kiok, Tan, Tse Siang, Wong, Sze Meng, Abdullah, Noor Hairiza, Liew, Chiat Fong, Luxuman, Lovenia, Mohd Zin, Nor Hafizah, Norddin, Muhamad Faiz, Alias, Raja Liza Raja, Wong, Juan Yong, Yong, Johnny, Bin Mustapha, Mohd Tarmimi, Chan, Weng Ken, Dzulkipli, Norizawati, Kuan, Pei Xuan, Lee, Yew Ching, Alias, Anita, Guok, Eng Ching, Jee, Chiun Chen, Ramon, Brian Rhadamantyne, Weng, Cheng Wong, Abd Ghafar, Fara Nur Idayu, Aziz, Faizal Zuhri, Hussain, Nabilah, Lee, Hooi Sean, Sukawi, Ismawaty, Woon, Yuan Liang, Abd Hadi, Husni Zaeem, Ahmad Azam, Ummi Azmira, Alias, Abdul Hafiz, Kesut, Saiful Aizar, Lee, Jun May, Ooi, Dar Vin, Sulaiman, Hetty Ayuni, Tengku Lih, Tengku Alini, Veerakumaran, Jeyaganesh, Rojas, Eder, Resendiz, Gerardo Esteban Alvarez, Zapata, Darcy Danitza Mari, Aguilar López, Julio Cesar Jesú, Flores, Armando Adolfo Alvarez, Amador, Juan Carlosc Bravo, Avila, Erendira Jocelin Dominguez, Aquino, Laura Patricia González, Rodriguez, Ricardo Lopez, Landa, Mariana Torre, Urias, Emma, Hollmann, Marku, Hulst, Abraham, Kirzner, Osne, Preckel, Benedikt, Koopman-van Gemert, Ankie, Buise, Marc, Tolenaar, Noortje, Weber, Eric, de Fretes, Jennifer, Houweling, Peter, Ormskerk, Patricia, Van Bommel, Jasper, Lance, Marcu, Smit-Fun, Valerie, van Zundert, Tom, Baas, Peter, de Boer, Hans Donald, Sprakel, Joost, Elferink-Vonk, Renske, Noordzij, Peter, van Zeggeren, Laura, Brand, Bastiaan, spanjersberg, Rob, ten Bokkel-Andela, Janneke, Numan, Janneke, van Klei, Wilton, van Zaane, 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Ganter, Donna Louise, McCann, Lloyd, Foley, Julia, Gilmour, Fiona, Lumsden, Rachelle, Moores, Mark, Olliff, Sue, Sardareva, Elitza, Tai, Joyce, Wikner, Matthew, Wong, Christopher, Chaddock, Mark, Czepanski, Carolyn, McKendry, Patrick, Polakovic, Daniel, Polakovich, Daniel, Robert, Axe, Tormo Belda, Margarita, Norton, Tracy, Alherz, Fadhel, Barneto, Lisa, Ramirez, Alberto, Sayeed, Ahmed, Smith, Nicola, Bennett, Cambell, McQuoid, Shane, Jansen, Tracy-Lee, Nico, Zin, Scott, John, Freschini, David, Freschini, Angela, Hopkins, Brian, Manson, Lara, Stoltz, Deon, Bates, Alexander, Davis, Simon, Freeman, Victoria, McGaughran, Lynette, Baskar Sharma, Swarna, Burrows, Tom, Byrne, Kelly, English, Duane, Johnson, Robert, Chai Law, Kiew, Manikkam, Brendon, Naidoo, Shaun, Rumball, Margot, Whittle, Nicola, Franks, Romilla, Gibson-Lapsley, Hannah, Salter, Ryan, Walsh, Dean, Cooper, Richard, Perry, Katherine, Obobolo, Amo, Sule, Umar Musa, Ahmad, Abdurrahman, Atiku, Mamuda, Mohammed, Alhassan Datti, Sarki, Adamu Muhammad, Adekola, Oyebola, Akanmu, Olanrewaju, Durodola, Akanmu, Olukoju, Olusegun, Raji, Victor, Olajumoke, Tokunbo, Oyebamiji, Emmanuel, Adenekan, Anthony, Adetoye, Adenekan, Faponle, Folayemi, Olateju, Simeon, Owojuyigbe, Afolabi, Talabi, Ademola, Adenike, Odewabi, Adewale, Badru, Collins, Nwokoro, Ezekiel, Emmanuel, Fatungase, Oluwabunmi Motunrayo, Grace, Anuforo, Sola, Sotannde, Stella, Ogunmuyiwa, Ademola, Adeyinka, Adeolu, Augustine A., Adigun, Tinuolac, Akinwale, Mukaila, Fasina, Oluyemi, Gbolahan, Olalere, Idowu, Olusola, Olonisakin, Rotimi Peter, Osinaike, Babatunde Babasola, Asudo, Felicia, Mshelia, Danladi, Abdur-Rahman, Lukman, Agodirin, Olayide, Bello, Jibril, Bolaji, Benjamin, Oyedepo, Olanrewaju Olubukola, Ezike, Humphrey, Iloabachie, Ikechukwu, Okonkwo, Ikemefuna, Onuora, Elia, Onyeka, Tonia, Ugwu, Innocent, Umeh, Friday, Alagbe-Briggs, Olubusola, Dodiyi-Manuel, Amabra, Echem, Richard, Obasuyi, Bright, Onajin-Obembe, Bisola, Bandeira, Maria Expedito, 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Kulikov, Alexander, Lubnin, Andrey, Grigoryev, Evgeny, Pugachev, Stanislav, Tolmasov, Alexander, Hussain, Ayyaz, Ilyina, Yana, Roshchina, Anna, Iurin, Aleksandr, Chazova, Elena, Dunay, Artem, Karelov, Alexey, Khvedelidze, Irina, Voldaeva, Olga, Belskiy, Vladislav, Dzhamullaev, Parvin, Grishkowez, Elena, Kretov, Vladimir, Levin, Valeriy, Molkov, Aleksandr, Puzanov, Sergey, Samoilenko, Aleksandr, Tchekulaev, Aleksandr, Tulupova, Valentina, Utkin, Ivan, Allorto, Nikki Leigh, Bishop, David Gray, Builu, Pierre Monji, Cairns, Carel, Dasrath, Ashish, de Wet, Jacque, den Hoedt, Marielle, Grey, Ben, Hayes, Morgan Philip, Küsel, Belinda Senta, Shangase, Nomcebo, Wise, Robert, Cacala, Sharon, Farina, Zane, Govindasamy, Vishendran, Kruse, Carl-Heinz, Lee, Carolyn, Marais, Leonard, Naidoo, Thinagrin Dhasarthun, Rajah, Chantal, Rodseth, Reitze Nil, Ryan, Lisa, von Rhaden, Richard, Adam, Suwayba, Alphonsus, Christella, Ameer, Yusuf, Anderson, Frank, Basanth, Sujith, Bechan, Sudha, Bhula, Chettan, 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Delgado García, David R., Zamudio, Diana, Garcia Del Valle, Santiago, Luz Serrano, M., Alonso, Eduardo, Anillo, Victor, Maseda, Emilio, Salgado, Patricia, Suarez, Lui, Suarez-de-la-Rica, Alejandro, Villagrán, María José, Alonso, José Ignacio, Cabezuelo, Estefania, Garcia-Saiz, Irene, Lopez del Moral, Olga, Martín, Silvia, Perez Gonzalez, Alba, Tovar Doncel, Sherezade, Vera, Martin Agüero, Ávila Sánchez, Francisco José, Castaño, Beatriz, Castaño Moreira, Beatriz, Flores Risco, Sahely, Paz Martín, Daniel, Pérez Martín, Fernando, Poza, Paloma, Ruiz, Adela, Serna Martínez, Wilson Fabio, Vicente, Bárbara Vázquez, Dominguez, Saul Velaz, Fernández, Salvador, Munoz-López, Alfonso, Bernat, Maria Jose, Mas, Arantxa, Planas, Kenneth, Jawad, Monir, Saeed, Yousif, Hedin, Annika, Levander, Helena, Holmström, Sandra, Lönn, David, Zoerner, Frank, Åkring, Irene, Widmark, Carl, Zettergren, Jan, Liljequist, Victor Aspelund, Nystrom, Lena, Odeberg-Wernerman, Suzanne, Oldner, Ander, Reje, Patrik, Lyckner, 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Amir, Shekar, Priya, Harden, Catherine, Hollands, Heidi, King, Angela, March, Linda, Minto, Gary, Patrick, Abigail, Waugh, Darren, Kumara, Paramesh, Simeson, Karen, Yarwood, Jamie, Browning, Julie, Hatton, Jonathan, Julian, Howe, Mitra, Atideb, Newton, Maria, Pernu, Pawan, Wilson, Alison, Commey, Thelma, Foot, Helen, Glover, Lyn, Gupta, Ajay, Lancaster, Nicola, Levin, Jill, Mackenzie, Felicity, Mestanza, Claire, Nofal, Emma, Pout, Lauren, Varden, Rosanna, Wild, Jonathan, Jones, Stephanie, Moreton, Sarah, Pulletz, Mark, Davies, Charlotte, Martin, Matthew, Thomas, Sian, Burns, Karen, McArthur, Carol, Patel, Panna, Lau, Gary, Rich, Natalie, Davis, Fiona, Lyons, Rachel, Port, Beth, Prout, Rachel, Smith, Christopher, Adelaja, Yemi, Bennett, Victoria, Bidd, Heena, Dumitrescu, Alexandra, Murphy, Jacqui Fox, Keen, Abigail, Mguni, Nhlanhla, Ong, Cheng, Adams, George, Boshier, Pier, Brown, Richard, Butryn, Izabella, Chatterjee, Jayanta, Freethy, Alexander, Lockwood, Geoffrey, Tsakok, Maria, Tsiligiannis, Sophia, Peat, William, Stephenson, Lorraine, Bradburn, Mike, Pick, Sara, Cunha, Pedro, Olagbaiye, Olufemi, Tayeh, Salim, Abernethy, Caroline, Balasubramaniam, Madhu, Bennett, Rachael, Bolton, David, Martinson, Victoria, Naylor, Charde, Bell, Stephanie, Heather, Blaylock, Kushakovsky, Vlad, Alcock, Liam, Alexander, Hazel, Anderson, Colette, Baker, Paul, Brookes, Morag, Cawthorn, Louise, Cirstea, Emanuel, Colling, Kerry, Coulter, Ian, Das, Suparna, Haigh, Kathryn, Hamdan, Alhafidz, Hugill, Keith, Kottam, Lucksy, Lisseter, Emily, Mawdsley, Matthew, McGivern, Julie, Padala, Krishnaveni, Phelps, Victoria, kumar, Vineshykaa Ramesh, Stewart, Kirsten, Towse, Kayley, Tregonning, Julie, Vahedi, Ali, Walker, Alycon, Baines, Duncan, Bilolikar, Anjali, Chande, Shiv, Copley, Edward, Dunk, Nigel, Kulkarni, Raghavendra, Kumar, Pawan, Metodiev, Yavor, Ncomanzi, Dumisani, Raithatha, Bhavesh, Raymode, Parizade, Szafranski, Jan, Twohey, Linda, Watt, Philip, Weatherall, Lucie, Weatherill, J., Whitman, Zoe, Wighton, Elinor, Abayasinghe, Chamika, Chan, Alexander, Darwish, Sharif, Gill, Jame, Glasgow, Emma, Hadfield, Daniel, Harris, Clair, Kochhar, Arun, Mellis, Clare, Pool, Andrew, Riozzi, Paul, Selman, Andrew, Smith, Emma-Jane, Vele, Liana, Gercek, Yuksel, Guy, Kramer, Holden, Dougla, Watson, Nichola, Whysall, Karen, Andreou, Prematie, Hales, Dawn, Thompson, Jonathan, Bowrey, Sarah, McDonald, Shara, Gilmore, Jemma, Hills, Vicky, Kelly, Chan, Kelly, Sinead, Lloyd, Geraint, Abbott, Tom, Gall, Lewi, Torrance, Hew, Vivian, Mark, Berntsen, Emer, Nolan, Tracey, Turner, Angu, Vohra, Akbar, Brown, Andrew, Clark, Richard, Coughlan, Elaine, Daniel, Conway, Patvardhan, Chinmay, Pearson, Rachel, Predeep, Sheba, Saad, Hesham, Shanmugam, Mohanakrishnan, Varley, Simon, Wylie, Katharine, Cooper, Lucy, Makowski, Arystarch, Misztal, Beata, Moldovan, Eliza, Pegg, Claire, Donovan, Andrew, Foot, Jayne, Large, Simon, Claxton, Andrew, Netke, Bhagyashree, Armstrong, Richard, Calderwood, Claire, Kwok, Andy, Mohr, Otto, Oyeniyi, Peter, Patnaik, Lisa, Post, Benjamin, Ali, Sarah, Arshad, Homa, Baker, Gerard, Brenner, Laura, Brincat, Maximilian, Brunswicker, Annemarie, Cox, Hannah, Cozar, Octavian Ionut, Durst, Alexander, Fengas, Lior, Flatt, Jim, Glister, Georgina, Narwani, Vishal, Photi, Evangelo, Rankin, Adeline, Rosbergen, Melissa, Tan, Mark, Beaton, Ceri, Horn, Rachel, Hunt, Jane, Rousseau, Guy, Stancombe, Lucia, Absar, Mohammed, Allsop, Joanne, Drinkwater, Zoe, Hodgkiss, Tracey, Smith, Kirsty, Brown, Jamie, Alexander-Sefre, Farhad, Campey, Lorraine, Dudgeon, Lucy, Hall, Kathryn, Hitchcock, Rachael, James, Lynne, Smith, Kate, Winstone, Ulrika, Ahmad, Norfaizan, Bauchmuller, Kri, Harrison, Jonathan, Jeffery, Holly, Miller, Duncan, Pinder, Angela, Pothuneedi, Sailaja, Rosser, Jonathan, Sanghera, Sumayer, Swift, Diane, Walker, Rachel, Bester, Delia, Cavanagh, Sarah, Cripps, Heather, Daniel, Harvey, Lynch, Julie, Paton, Alison, Pyke, Shirley, Scholefield, John, Whitworth, Helen, Bottrill, Fiona, Ramalingam, Ganesh, Webb, Stephen, Akerman, Nik, Antill, Philip, Bourner, Lynsey, Buckley, Sarah, Castle, Gail, Charles, Rob, Eggleston, Christopher, Foster, Rebecca, Gill, Satwant, Lindley, Kate, Lklouk, Mohamed, Lowery, Tracey, Martin, Oliver, Milne, David, O’Connor, Patrick, Ratcliffe, Andrew, Rose, Alastair, Smith, Annie, Varma, Sandeep, Ward, Jackie, Barcraft-Barnes, Helena, Camsooksai, Julie, Colvin, Carolyn, Reschreiter, Henrik, Tbaily, Lee, Venner, Nicola, Hamilton, Caroline, Kelly, Lewi, Toth-Tarsoly, Piroska, Dodsworth, Kerry, Foord, Denise, Gordon, Paul, Hawes, Elizabeth, Lamb, Nikki, Mouland, Johanna, Nightingale, Jeremy, Rose, Steve, Schrieber, Joe, Al ‘Amri, Khalid, Aladin, Hafiz, Arshad, Mohammed Asif, Barraclough, Jame, Bentley, Conor, Bergin, Colin, Carrera, Ronald, Clarkson, Aisling, Collins, Michelle, Cooper, Lauren, Denham, Samuel, Griffiths, Ewen, Ip, Peter, Jeyanthan, Somasundaram, Joory, Kavita, Kaur, Satwant, Marriott, Paul, Mitchell, Natalie, Nagaiah, Sukumar, Nilsson, Annette, Parekh, Nilesh, Pope, Martin, Seager, Joseph, Serag, Hosam, Tameem, Alifia, Thomas, Anna, Thunder, Joanne, Torrance, Andrew, Vohra, Ravinder, whitehouse, Arlo, Wong, Tony, Blunt, Mark, Wong, Kate, Giles, Julian, Reed, Isabelle, Weller, Debbie, Bell, Gillian, Birch, Julie, Damant, Rose, Maiden, Jane, Mewies, Clare, Prince, Claire, Radford, Jane, Balain, Birender, Banerjee, Robin, Barnett, Andrew, Burston, Ben, Davies, Kirsty, Edwards, Jayne, Evans, Chri, Ford, David, Gallacher, Pete, Hill, Simon, Jaffray, David, Karlakki, Sudheer, Kelly, Cormac, Kennedy, Julia, Kiely, Nigel, Lewthwaite, Simon, Marquis, Chri, Ockendon, Matthew, Phillips, Stephen, Pickard, Simon, Richardson, Jame, Roach, Richard, Smith, Tony, Spencer-Jones, Richard, Steele, Niall, Steen, Julie, Van Liefland, Marck, White, Steve, Faulds, Matthew, Harris, Meredyth, Kelly, Carrie, Nicol, Scott, Pearson, Sally Anne, Chukkambotla, Srikanth, Andrew, Alyson, Attrill, Elizabeth, Campbell, Graham, Datson, Amanda, Fouracres, Anna, Graterol, Juan, Graves, Lynne, Hong, Bosun, Ishimaru, Alexander, Karthikeyan, Arvind, King, Helen, Lawson, Tom, Lee, Gregory, Lyons, Saoirse, Macalister Hall, Andrew, Mathoulin, Sophie, Mcintyre, Eilidh, Mclaughlin, Danny, Mulcahy, Kathleen, Ratcliffe, Anna, Robbins, Jame, Sung, Weilin, Tayo, Adeoluwa, Trembath, Lisa, Venugopal, Suneetha, Walker, Robert, Wigmore, Geoffrey, Boereboom, Catherine, Downes, Charlotte, Humphries, Ryan, Melbourne, Susan, Smith, Coral, Tou, Samson, Ullah, Shafa, Batchelor, Nick, Boxall, Leigh, Broomby, Rupert, Deen, Tariq, Hellewell, Alistair, Helliwell, Laurence, Hutchings, Melanie, Hutchins, David, Keenan, Samantha, Mackie, Donna, Donna, Alison, Smith, France, Stone, Lucy, Thorpe, Kevin, Wassall, Richard, Woodgate, Andrew, Baillie, Shelley, Campbell, Tara, James, Sarah, King, Chri, Marques de Araujo, Daniela, Martin, Daniel, Morkane, Clare, Neely, Julia, Rajendram, Rajkumar, Burton, Megan, James, Kathryn, Keevil, Edward, Minik, Orsolya, Morgan, Jenna, Musgrave, Anna, Rajanna, Harish, Roberts, Tracey, Adamson, Michael, Jumbe, Sandra, Kendall, Jennie, Muthuswamy, Mohan Babu, Anderson, Charlotte, Cruikshanks, Andrew, Wrench, Ian, Zeidan, Lisa, Ardern, Diane, Harris, Benjamin, Hellstrom, Johanna, Martin, Jane, Thomas, Richard, Varsani, Nimu, Wrey Brown, Caroline, Docherty, Philip, Gillies, Michael, McGregor, Euan, Usher, Helen, Craig, Jayne, Smith, Andrew, Ahmad, Tahania, Bodger, Phoebe, Creary, Thai, Fowler, Alexander, Hewson, Ru, Ijuo, Eke, Jones, Timothy, Kantsedikas, Ilya, Lahiri, Sumitra, McLean, Aaron Lawson, Niebrzegowska, Edyta, Phull, Mandeep, Wang, Difei, Wickboldt, Nadine, Baldwin, Jacqueline, Doyle, Donna, Mcmullan, Sean, Oladapo, Michelle, Owen, Thoma, Williams, Alexandra, Daniel, Hull, Gregory, Peter, Husain, Tauqeer, Kirk-Bayley, Justin, Mathers, Edward, Montague, Laura, White, Stuart, Avis, Joanne, Cook, Tim, Dali-Kemmery, Lola, Kerslake, Ian, Lambourne, Victoria, Pearson, Annabel, Boyd, Christine, Callaghan, Mark, Lawson, Cathy, McCrossan, Roopa, Nesbitt, Vanessa, O’connor, Laura, Scott, Julia, Sinclair, Rhona, Farid, Nahla, Morgese, Ciro, Bhatia, Kailash, Karmarkar, Swati, Ahmed, Jamil, Branagan, Graham, Hutton, Monica, Swain, Andrew, Brookes, Jamie, Cornell, Jonathan, Dolan, Rachael, Hulme, Jonathan, Jansen van Vuuren, Amanda, Jowitt, Tom, Kalashetty, Gunasheela, Lloyd, Fran, Patel, Kiran, Sherwood, Nichola, Brown, Lynne, Chandler, Ben, Deighton, Kerry, Emma, Temlett, Haunch, Kirsty, Cheeseman, Michelle, Dent, Kathy, Garg, Sanjeev, Gray, Carol, Hood, Marion, Jones, Dawn, Juj, Joanne, Rao, Roshan, Walker, Tara, Al Anizi, Mashel, Cheah, Clarissa, Cheing, Yushio, Coutinho, Francisco, Gondo, Prisca, Hadebe, Bernard, Onie Hove, Mazvangu, khader, Ahamed, Krishnachetty, Bobby, Rhodes, Karen, Sokhi, Jagdish, Baker, Katie-Anne, Bertram, Wendy, Looseley, Alex, Mouton, Ronelle, Arnold, Glenn, Arya, Shobhit, Balfoussia, Danai, Baxter, Linden, Harris, Jame, Jones, Craig, Knaggs, Alison, Markar, Sheraz, Perera, Anisha, Scott, Alasdair, Shida, Asako, Sirha, Ravneet, Wright, Sally, Frost, Victoria, Gray, Catherine, MacGregor, Mark, Andrews, Emma, Arrandale, Lindsay, Barrett, Stephen, Cifra, Elna, Cooper, Mariese, Dragnea, Drago, Elna, Cifra, Maclean, Jennifer, Meier, Sonja, Milliken, Donald, Munns, Christopher, Ratanshi, Nadir, Salvana, Abegail, Watson, Anthony, Ali, Hani, Campbell, Gill, Critchley, Rebecca, Hicks, Catherine, Liddle, Alison, Pass, Marc, Ritchie, Charlotte, Thomas, Charlotte, Too, Lingxi, Welsh, Sarah, Gill, Talvinder, Johnson, Joanne, Reed, Joanne, Davis, Edward, Papadopoullos, Sam, Attwood, Clare, Biffen, Andrew, Boulton, Kerenza, Gray, Sophie, Hay, David, Mills, Sarah, Montgomery, Jane, Riddell, Rory, Simpson, Jame, Bhardwaj, Neeraj, Paul, Elaine, Uwubamwen, Nosakhare, Alexander, Maini, Arrich, Jame, Arumugam, Swarna, Blackwood, Dougla, Boggiano, Victoria, Brown, Robyn, Lam Chan, Yik, Chatterjee, Devnandan, Chhabra, Ashok, Christian, Rachel, Costelloe, Hannah, Coxwell Matthewman, Madeline, Dalton, Emma, Darko, Julia, Davari, Maria, Dave, Tejal, Deacon, Matthew, Deepak, Shantal, Edmond, Holly, Ellis, Jessica, El-Sayed, Ahmed, Eneje, Philip, English, Rose, Ewe, Renee, Foers, William, Franklin, John, Gallego, Laura, Garrett, Emily, Goldberg, Olivia, Goss, Harry, Greaves, Rosanna, Harris, Rudy, Hennings, Charle, Jones, Eleanor, Kamali, Nelson, Kokkinos, Naomi, Lewis, Cary, Lignos, Leda, Malgapo, Evaleen Victoria, Malik, Rizwana, Milne, Andrew, Mulligan, John-Patrick, Nicklin, Philippa, Palipane, Natasha, Parsons, Thoma, Piper, Rebecca, Prakash, Rohan, Ramesh, Byron, Rasip, Sarah, Reading, Jacob, Rela, Mariam, Reyes, Anna, Robert, Stephen, Rooms, Martin, Shah, Karishma, Simons, Henry, Solanki, Shalil, Spowart, Emma, Stevens, Amy, Thomas, Christopher, Waggett, Helena, Yassaee, Arrash, Kennedy, Anthony, Scott, Sara, Somanath, Sameer, Berg, Andrew, Hernandez, Miguel, Nanda, Rajesh, Tank, Ghanshyambhai, Wilson, Natalie, 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Garg, A., Karpate, S., O'Hara, C., Troko, J., Angus, K., Bradley, J., Brennan, E., Brooks, C., Brown, J., Brown, G., Finch, A., Gratrix, K., Hesketh, S., Hill, G., Jeffs, C., Morgan, M., Pemberton, C., Slawson, N., Spickett, H., Swarbrick, G., Van Duyvenvoorde, G., Brennan, A., Briscoe, R., Cooper, S., Lawton, T., Northey, M., Senaratne, R., Stanworth, H., Burrows, L., Cain, H., Craven, R., Davies, K., Jonas, A., Pachucki, M., Walkden, G., Davies, H., Gudaca, M., Hobrok, M., Arawwawala, D., Fergey, L., Gardiner, M., Gunn, J., Johnson, L., Lofting, A., Lyle, A., Mc Neela, F., Smolen, S., Topliffe, J., Williams, S., Bland, M., Kaura, V., Lanka, P., Naylor, C., Ahmed, A., Myatt, J., Shenoy, R., Soon, W.C., Tan, J., Karadia, S., Self, J., Durant, E., Tripathi, S., Bullock, C., Ghosh, A., Hughes, T., Zsisku, L., Bengeri, S., Cowton, A., Khalid, M.S., Limb, J., McAdam, C., Porritt, M., Rafi, M.A., Shekar, P., Harden, C., Hollands, H., King, A., March, L., Minto, G., Patrick, A., Waugh, D., Kumara, P., Simeson, K., Yarwood, J., Browning, J., Hatton, J., Julian, H., Mitra, A., Newton, M., Pernu, P., Wilson, A., Commey, T., Foot, H., Glover, L., Gupta, A., Lancaster, N., Levin, J., Mackenzie, F., Mestanza, C., Nofal, E., Pout, L., Varden, R., Wild, J., Jones, S., Moreton, S., Pulletz, M., Davies, C., Martin, M., Thomas, S., Burns, K., McArthur, C., Patel, P., Lau, G., Rich, N., Davis, F., Lyons, R., Port, B., Prout, R., Smith, C., Adelaja, Y., Bennett, V., Bidd, H., Dumitrescu, A., Murphy, J.F., Keen, A., Mguni, N., Ong, C., Adams, G., Boshier, P., Brown, R., Butryn, I., Chatterjee, J., Freethy, A., Lockwood, G., Tsakok, M., Tsiligiannis, S., Peat, W., Stephenson, L., Bradburn, M., Pick, S., Cunha, P., Olagbaiye, O., Tayeh, S., Abernethy, C., Balasubramaniam, M., Bennett, R., Bolton, D., Martinson, V., Bell, S., Heather, B., Kushakovsky, V., Alcock, L., Alexander, H., Anderson, C., Baker, P., Brookes, M., Cawthorn, L., Cirstea, E., Colling, K., Coulter, I., Das, S., Haigh, K., Hamdan, A., Hugill, K., Kottam, L., Lisseter, E., Mawdsley, M., McGivern, J., Padala, K., Phelps, V., Kumar, V.R., Stewart, K., Towse, K., Tregonning, J., Vahedi, A., Walker, A., Baines, D., Bilolikar, A., Chande, S., Copley, E., Dunk, N., Kulkarni, R., Kumar, P., Metodiev, Y., Ncomanzi, D., Raithatha, B., Raymode, P., Szafranski, J., Twohey, L., Watt, P., Weatherall, L., Whitman, Z., Wighton, E., Abayasinghe, C., Chan, A., Darwish, S., Gill, J., Glasgow, E., Hadfield, D., Harris, C., Kochhar, A., Mellis, C., Pool, A., Riozzi, P., Selman, A., Smith, E.J., Vele, L., Gercek, Y., Guy, K., Holden, D., Watson, N., Whysall, K., Andreou, P., Hales, D., Thompson, J., Bowrey, S., McDonald, S., Gilmore, J., Hills, V., Kelly, C., Kelly, S., Lloyd, G., Abbott, T., Gall, L., Torrance, H., Vivian, M., Berntsen, E., Nolan, T., Turner, A., Vohra, A., Brown, A., Clark, R., Coughlan, E., Daniel, C., Patvardhan, C., Pearson, R., Predeep, S., Saad, H., Shanmugam, M., Varley, S., Wylie, K., Cooper, L., Makowski, A., Misztal, B., Moldovan, E., Pegg, C., Donovan, A., Foot, J., Large, S., Claxton, A., Netke, B., Armstrong, R., Calderwood, C., Kwok, A., Mohr, O., Oyeniyi, P., Patnaik, L., Post, B., Ali, S., Arshad, H., Baker, G., Brenner, L., Brincat, M., Brunswicker, A., Cox, H., Cozar, O.I., Durst, A., Fengas, L., Flatt, J., Glister, G., Narwani, V., Photi, E., Rankin, A., Rosbergen, M., Beaton, C., Horn, R., Hunt, J., Rousseau, G., Stancombe, L., Absar, M., Allsop, J., Drinkwater, Z., Hodgkiss, T., Smith, K., Alexander-Sefre, F., Campey, L., Dudgeon, L., Hall, K., Hitchcock, R., James, L., Winstone, U., Ahmad, N., Bauchmuller, K., Harrison, J., Jeffery, H., Miller, D., Pinder, A., Pothuneedi, S., Rosser, J., Sanghera, S., Swift, D., Walker, R., Bester, D., Cavanagh, S., Cripps, H., Daniel, H., Lynch, J., Pyke, S., Scholefield, J., Whitworth, H., Bottrill, F., Ramalingam, G., Webb, S., Akerman, N., Antill, P., Bourner, L., Buckley, S., Castle, G., Charles, R., Eggleston, C., Foster, R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M.A., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., Whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Balain, B., Banerjee, R., Barnett, A., Burston, B., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Nicol, S., Pearson, S.A., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Macalister Hall, A., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Donna, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., Marques de Araujo, D., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M.B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Wrey Brown, C., Docherty, P., Gillies, M., McGregor, E., Usher, H., Craig, J., Ahmad, T., Bodger, P., Creary, T., Fowler, A., Ijuo, E., Jones, T., Kantsedikas, I., Lahiri, S., McLean, A.L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., McCrossan, R., Nesbitt, V., O'connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Jansen van Vuuren, A., Jowitt, T., Kalashetty, G., Lloyd, F., Patel, K., Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Onie Hove, M., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K.A., Bertram, W., Looseley, A., Mouton, R., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., MacGregor, M., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Salvana, A., Watson, A., Ali, H., Critchley, R., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Lam Chan, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Coxwell Matthewman, M., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E.V., Malik, R., Milne, A., Mulligan, J.P., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Robert, S., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Skinner, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., McDonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L.L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Zhu, X., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: Male, HSJ UCI, Critical Care and Intensive Care Medicine, law.invention, Perioperative Care/methods, 0302 clinical medicine, Surgical procedures, 030202 anesthesiology, law, Critical care/utilisation, Postoperative care/methods, Postoperative care/statistics and numerical data, Surgical procedures, operative/mortality, statistics and numerical data, Prospective Studies, Postoperative Period, Postoperative care/methods, education.field_of_study, Postoperative care/method, Elective Surgical Procedures/mortality, fluid output, Middle Aged, fluid administration, Intensive care unit, Hospitalization, Length of Stay/statistics & numerical data, operative/mortality, Intensive Care Units/statistics & numerical data, outcome, Female, Elective Surgical Procedure, Human, Adult, medicine.medical_specialty, Logistic Model, Postoperative care/statistics and numerical data, Critical care/utilisation, Population, Intensive Care Unit, Elective Surgical Procedures/statistics & numerical data, Hospitalization/statistics & numerical data, Humans, Logistic Models, Surgical procedures, operative/mortality, Postoperative care, methods, Perioperative Care, NO, 03 medical and health sciences, Anesthesiology, Intensive care, medicine, Elective surgery, Intensive care medicine, education, business.industry, 030208 emergency & critical care medicine, Perioperative, Length of Stay, Clinical trial, Prospective Studie, septic shock, business
Abstract: PURPOSE: As global initiatives increase patient access to surgical treatments, there is a need to define optimal levels of perioperative care. Our aim was to describe the relationship between the provision and use of critical care resources and postoperative mortality. METHODS: Planned analysis of data collected during an international 7-day cohort study of adults undergoing elective in-patient surgery. We used risk-adjusted mixed-effects logistic regression models to evaluate the association between admission to critical care immediately after surgery and in-hospital mortality. We evaluated hospital-level associations between mortality and critical care admission immediately after surgery, critical care admission to treat life-threatening complications, and hospital provision of critical care beds. We evaluated the effect of national income using interaction tests. RESULTS: 44,814 patients from 474 hospitals in 27 countries were available for analysis. Death was more frequent amongst patients admitted directly to critical care after surgery (critical care: 103/4317 patients [2%], standard ward: 99/39,566 patients [0.3%]; adjusted OR 3.01 [2.10-5.21]; p < 0.001). This association may differ with national income (high income countries OR 2.50 vs. low and middle income countries OR 4.68; p = 0.07). At hospital level, there was no association between mortality and critical care admission directly after surgery (p = 0.26), critical care admission to treat complications (p = 0.33), or provision of critical care beds (p = 0.70). Findings of the hospital-level analyses were not affected by national income status. A sensitivity analysis including only high-risk patients yielded similar findings. CONCLUSIONS: We did not identify any survival benefit from critical care admission following surgery. info:eu-repo/semantics/publishedVersion
Published: 2017
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21. The effect of a high-polyphenol Mediterranean diet (Green-MED) combined with physical activity on age-related brain atrophy: the Dietary Intervention Randomized Controlled Trial Polyphenols Unprocessed Study (DIRECT PLUS)

Author: Alon Kaplan, Hila Zelicha, Anat Yaskolka Meir, Ehud Rinott, Gal Tsaban, Gidon Levakov, Ofer Prager, Moti Salti, Yoram Yovell, Jonathan Ofer, Sebastian Huhn, Frauke Beyer, Veronica Witte, Arno Villringer, Nachshon Meiran, Tamar B Emesh, Peter Kovacs, Martin von Bergen, Uta Ceglarek, Matthias Blüher, Michael Stumvoll, Frank B Hu, Meir J Stampfer, Alon Friedman, Ilan Shelef, Galia Avidan, and Iris Shai
Subjects: Male, Nutrition and Dietetics, Tea, Medicine (miscellaneous), Brain, Humans, Polyphenols, Female, Juglans, Atrophy, Middle Aged, Diet, Mediterranean, Exercise
Abstract: Background: The effect of diet on age-related brain atrophy is largely unproven. Objectives: We aimed to explore the effect of a Mediterranean diet (MED) higher in polyphenols and lower in red/processed meat (Green-MED diet) on age-related brain atrophy. Methods: This 18-mo clinical trial longitudinally measured brain structure volumes by MRI using hippocampal occupancy score (HOC) and lateral ventricle volume (LVV) expansion score as neurodegeneration markers. Abdominally obese/dyslipidemic participants were randomly assigned to follow 1) healthy dietary guidelines (HDG), 2) MED, or 3) Green-MED diet. All subjects received free gym memberships and physical activity guidance. Both MED groups consumed 28 g walnuts/d (+440 mg/d polyphenols). The Green-MED group consumed green tea (3-4 cups/d) and Mankai (Wolffia-globosa strain, 100 g frozen cubes/d) green shake (+800 mg/d polyphenols). Results: Among 284 participants (88% men; mean age: 51 y; BMI: 31.2 kg/m2; APOE-ε4 genotype = 15.7%), 224 (79%) completed the trial with eligible whole-brain MRIs. The pallidum (-4.2%), third ventricle (+3.9%), and LVV (+2.2%) disclosed the largest volume changes. Compared with younger participants, atrophy was accelerated among those ≥50 y old (HOC change: -1.0% ± 1.4% compared with -0.06% ± 1.1%; 95% CI: 0.6%, 1.3%; P < 0.001; LVV change: 3.2% ± 4.5% compared with 1.3% ± 4.1%; 95% CI: -3.1%, -0.8%; P = 0.001). In subjects ≥ 50 y old, HOC decline and LVV expansion were attenuated in both MED groups, with the best outcomes among Green-MED diet participants, as compared with HDG (HOC: -0.8% ± 1.6% compared with -1.3% ± 1.4%; 95% CI: -1.5%, -0.02%; P = 0.042; LVV: 2.3% ± 4.7% compared with 4.3% ± 4.5%; 95% CI: 0.3%, 5.2%; P = 0.021). Similar patterns were observed among younger subjects. Improved insulin sensitivity over the trial was the parameter most strongly associated with brain atrophy attenuation (P < 0.05). Greater Mankai, green tea, and walnut intake and less red and processed meat were significantly and independently associated with reduced HOC decline (P < 0.05). Elevated urinary concentrations of the polyphenols urolithin-A (r = 0.24; P = 0.013) and tyrosol (r = 0.26; P = 0.007) were significantly associated with lower HOC decline. Conclusions: A Green-MED (high-polyphenol) diet, rich in Mankai, green tea, and walnuts and low in red/processed meat, is potentially neuroprotective for age-related brain atrophy.This trial was registered at clinicaltrials.gov as NCT03020186.
Published: 2021

22. Intraoperative Awareness With Recall

Author: Shagun Mathur, Michael S. Avidan, Anna Maria Bombardieri, Arbi Ben Abdallah, Anshuman Sharma, Troy S. Wildes, and Andrea Soares
Subjects: Adult, Male, medicine.medical_specialty, Sedation, media_common.quotation_subject, MEDLINE, Intraoperative Awareness, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Surveys and Questionnaires, medicine, Paralysis, Humans, Aged, media_common, business.industry, Middle Aged, Distress, Anesthesiology and Pain Medicine, Feeling, Mental Recall, Cohort, Physical therapy, Female, medicine.symptom, business, 030217 neurology & neurosurgery, Cohort study
Abstract: Background Unintended intraoperative awareness with recall (AWR) is a potential complication of general anesthesia. Patients typically report recollections of (1) hearing sounds or conversations, (2) being unable to breathe or move, (3), feeling pain, and/or (4) experiencing emotional distress. The purpose of the current study was to identify and further characterize AWR experiences identified through postoperative surveys of a large unselected adult surgical cohort. Methods This is a substudy of a prospective registry study, which surveys patients on their health and well-being after surgery. Responses to 4 questions focusing on AWR were analyzed. Patients who reported AWR with pain, paralysis, and/or distress were contacted by telephone to obtain more information about their AWR experience. The interview results for patients who received general anesthesia were sent to 3 anesthesiologists, who adjudicated the reported AWR episodes. Results Of 48,151 surveys sent, 17,875 patient responses were received. Of these respondents, 622 reported a specific memory from the period between going to sleep and waking up from perceived general anesthesia and 282 of these reported related pain, paralysis, and/or distress. An attempt was made to contact these 282 patients, and 149 participated in a telephone survey. Among the 149 participants, 87 endorsed their prior report of AWR. However, only 22 of these patients had received general anesthesia, while 51 received only sedation and 14 received regional anesthesia. Three anesthesiologists independently adjudicated the survey results of the 22 general anesthesia cases and assigned 6 as definite AWR, 8 as possible AWR, and 8 as not AWR episodes. Of the 65 patients who confirmed their report of AWR after regional or sedation anesthesia, 37 (31 with sedation and 6 with regional anesthesia) had not expected to be conscious during surgery. Conclusions The complication of AWR continues to occur during intended general anesthesia. Many reports of AWR episodes occur in patients receiving sedation or regional anesthesia and relate to incorrect expectations regarding anesthetic techniques and conscious experiences, representing a potential target for intervention.
Published: 2019
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23. The Effect of Repeated Versus Initial Procalcitonin Measurements on Diagnosis of Infection in the Intensive Care Setting

Author: Alexander Avidan, Eden Ohev-Zion, Sheldon Stohl, Matan J. Cohen, Phillip D. Levin, Ronit Cohen-Poraduso, Shmuel Benenson, Allon E. Moses, Samer Tannus, and Charles L. Sprung
Subjects: Adult, Male, medicine.medical_specialty, Time Factors, Critical Care, Procalcitonin, Single test, law.invention, Antimicrobial Stewardship, 03 medical and health sciences, 0302 clinical medicine, Predictive Value of Tests, 030202 anesthesiology, law, Internal medicine, Intensive care, parasitic diseases, Humans, Medicine, Prospective Studies, Prospective cohort study, Aged, business.industry, Reproducibility of Results, Bacterial Infections, Middle Aged, Intensive care unit, Confidence interval, Anti-Bacterial Agents, Intensive Care Units, Anesthesiology and Pain Medicine, Predictive value of tests, Female, Observational study, business, Biomarkers, hormones, hormone substitutes, and hormone antagonists, 030217 neurology & neurosurgery
Abstract: Procalcitonin (PCT) measurement has been proposed to direct antibiotic use. We examined whether repeated PCT measurements (0, 6, and/or 12 hours) versus the initial measurement only (time 0) increased the sensitivity and specificity of PCT for diagnosing infection in intensive care unit patients. Infection was identified in 67/176 (38%) patients. The sensitivity of repeated versus the initial PCT measurement (with a cutoff value 0.5 ng/mL) was 52/67 (77%; 95% confidence interval [CI], 66%-87%) vs 46/67 (69%; 95% CI, 56%-79%; P = .04) and specificity 60/109 (55%; 95% CI, 45%-65%) vs 59/109 (54%; 95% CI, 44%-64%; P = 1.0). Repeat PCT evaluations over 12 hours did not provide a clinically significant improvement in diagnostic accuracy when compared to the initial single test.
Published: 2019
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24. The relationship between obstructive sleep apnoea and postoperative delirium and pain: an observational study of a surgical cohort

Author: A. Ben Abdallah, Vanessa L. Kronzer, Sherry L. McKinnon, William Shun Tzeng, Simon Haroutounian, B. Arrington, Michael S. Avidan, and Patricia Strutz
Subjects: Adult, Male, medicine.medical_specialty, Visual analogue scale, Logistic regression, Cohort Studies, Young Adult, Emergence Delirium, Risk Factors, Surveys and Questionnaires, Internal medicine, medicine, Humans, Mass Screening, Risk factor, Aged, Pain Measurement, Retrospective Studies, Aged, 80 and over, Pain, Postoperative, Sleep Apnea, Obstructive, business.industry, Incidence, Incidence (epidemiology), Odds ratio, Middle Aged, nervous system diseases, Anesthesiology and Pain Medicine, Cohort, Delirium, Female, Observational study, medicine.symptom, business
Abstract: Patients with obstructive sleep apnoea are at increased risk of adverse postoperative outcomes, such as cardiac and respiratory complications. It has been hypothesised that obstructive sleep apnoea also increases the risk for postoperative delirium and acute postoperative pain. We conducted a retrospective, observational study investigating the relationship of obstructive sleep apnoea with postoperative delirium and acute postoperative pain severity. Patients were classified as being at high risk for obstructive sleep apnoea if they had been diagnosed with this condition, or if they were positive for more than four factors using the 'STOP-BANG' screening tool. Adjusted logistic regression was used to investigate the association between obstructive sleep apnoea and postoperative delirium, and multivariable linear regression to study the relationship between obstructive sleep apnoea and postoperative pain severity. The incidence of postoperative delirium was 307 in 1441 patients (21.3%; 95%CI 19.2-23.5%). In unadjusted analysis, high risk for obstructive sleep apnoea was associated with delirium, with an odds ratio (95%CI) of 1.77 (1.22-2.57; p = 0.003). After adjustment for pre-specified variables, the association was not statistically significant with odds ratio 1.34 (0.80-2.23; p = 0.27). The mean (SD) maximum pain (resting or provoked) reported for the entire cohort was 63.8 (27.9) mm on a 0-100 mm visual analogue scale. High risk for obstructive sleep apnoea was not associated with postoperative pain severity (β-coefficient 2.82; 95%CI, -2.34-7.97; p = 0.28). These findings suggest that obstructive sleep apnoea is unlikely to be a strong risk factor for postoperative delirium or acute postoperative pain severity.
Published: 2019
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25. Minimal Recognizable Configurations Elicit Category-selective Responses in Higher Order Visual Cortex

Author: Daniel Harari, Galia Avidan, Marlene Behrmann, Yael Holzinger, and Shimon Ullman
Subjects: Adult, Male, Cognitive Neuroscience, Brain mapping, Young Adult, medicine, Humans, Set (psychology), Visual Cortex, Brain Mapping, Neural correlates of consciousness, business.industry, Cognitive neuroscience of visual object recognition, Brain, Recognition, Psychology, Pattern recognition, Fusiform face area, Magnetic Resonance Imaging, Visual cortex, medicine.anatomical_structure, Pattern Recognition, Visual, Pattern recognition (psychology), Female, Transverse occipital sulcus, Artificial intelligence, Psychology, business, Photic Stimulation
Abstract: Visual object recognition is performed effortlessly by humans notwithstanding the fact that it requires a series of complex computations, which are, as yet, not well understood. Here, we tested a novel account of the representations used for visual recognition and their neural correlates using fMRI. The rationale is based on previous research showing that a set of representations, termed “minimal recognizable configurations” (MIRCs), which are computationally derived and have unique psychophysical characteristics, serve as the building blocks of object recognition. We contrasted the BOLD responses elicited by MIRC images, derived from different categories (faces, objects, and places), sub-MIRCs, which are visually similar to MIRCs, but, instead, result in poor recognition and scrambled, unrecognizable images. Stimuli were presented in blocks, and participants indicated yes/no recognition for each image. We confirmed that MIRCs elicited higher recognition performance compared to sub-MIRCs for all three categories. Whereas fMRI activation in early visual cortex for both MIRCs and sub-MIRCs of each category did not differ from that elicited by scrambled images, high-level visual regions exhibited overall greater activation for MIRCs compared to sub-MIRCs or scrambled images. Moreover, MIRCs and sub-MIRCs from each category elicited enhanced activation in corresponding category-selective regions including fusiform face area and occipital face area (faces), lateral occipital cortex (objects), and parahippocampal place area and transverse occipital sulcus (places). These findings reveal the psychological and neural relevance of MIRCs and enable us to make progress in developing a more complete account of object recognition.
Published: 2019
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26. Emotional cues differently modulate visual processing of faces and objects

Author: Bat-Sheva Hadad, Galia Avidan, Elite Mardo, and Sivan Schwartz
Subjects: Adult, Male, Visual perception, genetic structures, media_common.quotation_subject, Emotions, Stimulus (physiology), 050105 experimental psychology, Arousal, Visual processing, Young Adult, Perception, medicine, Humans, Attention, 0501 psychology and cognitive sciences, General Psychology, media_common, Facial expression, 05 social sciences, Emotional stimuli, Facial Expression, Visual Perception, Anxiety, Female, Cues, medicine.symptom, Psychology, Cognitive psychology
Abstract: Ample evidence suggests that emotion affects visual perception. Here we asked how arousal, induced by emotional stimuli and modulated by anxiety trait, biases competition among stimuli to favor the perceptually conspicuous ones. We first demonstrated that negatively arousing pictures impaired subsequent discrimination of cars, but not the discrimination of faces, among individuals with high-trait anxiety. To directly demonstrate the role of attention in the emotional modulations of visual perception, we used a modified exogenous cuing task, showing that for anxious individuals, a negatively arousing cue elicited cost when processing cars but not faces. These results indicate that arousal biases attention toward perceptually salient stimuli, allowing those with high-trait anxiety to disengage attention from an arousing stimulus more easily when it is followed by a face. The results suggest that attention modulates the effects of emotion on perception, leading to higher resilience of high-priority stimuli to arousal-biased competition. (PsycINFO Database Record (c) 2019 APA, all rights reserved).
Published: 2019
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27. Dynamic Cortical Connectivity during General Anesthesia in Healthy Volunteers

Author: Duan, Li, Phillip E, Vlisides, Max B, Kelz, Michael S, Avidan, George A, Mashour, and Ben J A, Palanca
Subjects: Adult, Male, media_common.quotation_subject, Anesthesia, General, Electroencephalography, Young Adult, 03 medical and health sciences, 0302 clinical medicine, 030202 anesthesiology, Healthy volunteers, medicine, Humans, Young adult, Propofol, media_common, Cerebral Cortex, Isoflurane, medicine.diagnostic_test, business.industry, Unconsciousness, Healthy Volunteers, Burst suppression, Anesthesiology and Pain Medicine, Anesthesia, Anesthetics, Inhalation, Female, Nerve Net, medicine.symptom, Consciousness, business, Anesthetics, Intravenous, 030217 neurology & neurosurgery, medicine.drug
Abstract: Editor’s Perspective What We Already Know about This Topic What This Article Tells Us That Is New Background Recent studies of anesthetic-induced unconsciousness in healthy volunteers have focused on functional brain connectivity patterns, but the protocols rarely parallel the depth and duration of surgical anesthesia. Furthermore, it is unknown whether there is a single functional connectivity pattern that correlates with general anesthesia for the duration of prolonged anesthetic exposure. Methods The authors analyzed electroencephalographic data in 30 healthy participants who underwent induction of anesthesia with propofol followed by 3 h of isoflurane anesthesia at age-adjusted 1.3 minimum alveolar concentration. Functional connectivity was assessed by frequency-resolved weighted phase lag index between frontal and parietal channels and between prefrontal and frontal channels, which were classified into a discrete set of states through k-means cluster analysis. Temporal dynamics were evaluated by the occurrence rate and dwell time distribution for each state as well as the transition probabilities between states. Results Burst suppression was present, with mean suppression ratio reducing from 44.8 ± 32.3% to 14.0 ± 20.2% (mean ± SD) during isoflurane anesthesia (P < 0.001). Aside from burst suppression, eight connectivity states were classified by optimizing the reproducibility of clustering solutions, with each characterized by distinct properties. The temporal progression of dominant states revealed a successive shifting trajectory from the state associated with alpha frontal-parietal connectivity to those associated with delta and alpha prefrontal-frontal connectivity during induction, which was reversed during emergence. Cortical connectivity was dynamic during maintenance period, and it was more probable to remain in the same state (82.0 ± 8.3%) than to switch to a different state (P < 0.001). However, transitions to other states were structured, i.e., occurred more frequently than expected by chance. Conclusions Anesthesia-induced alterations of functional connectivity are dynamic despite the stable and prolonged administration of isoflurane, in the absence of any noxious stimuli. Changes in connectivity over time will likely yield more information as a marker or mechanism of surgical anesthesia than any single pattern.
Published: 2019
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28. Association Between Hyperbaric Bupivacaine Dose and Maternal Hypotension: Retrospective Database Study of 8226 Women Undergoing Cesarean Delivery Under Spinal Anesthesia

Author: Alexander Avidan, David Knigin, Carolyn F Weiniger, Frederic Deutsch, Michael Heesen, and N. Hilber
Subjects: Adult, Time Factors, Databases, Factual, Blood Pressure, Anesthesia, Spinal, Risk Assessment, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Risk Factors, 030202 anesthesiology, Management of Technology and Innovation, medicine, Anesthesia, Obstetrical, Humans, Anesthetics, Local, Retrospective Studies, Dose-Response Relationship, Drug, Cesarean Section, business.industry, Incidence (epidemiology), Gestational age, Retrospective cohort study, Odds ratio, medicine.disease, Bupivacaine, Confidence interval, Treatment Outcome, Anesthesiology and Pain Medicine, Blood pressure, Maternal Hypotension, Anesthesia, Hypertensive disease of pregnancy, Female, Hypotension, business, 030217 neurology & neurosurgery
Abstract: Low-dose (≤8 mg) hyperbaric bupivacaine for spinal anesthesia during cesarean delivery results in reduced efficacy, yet as a secondary outcome was associated with reduced frequency of spinal-induced hypotension. Our primary aim was to investigate the relationship between hyperbaric bupivacaine dose and the occurrence of spinal-induced hypotension for cesarean delivery.Retrospective study of cesarean delivery under spinal or combined spinal anesthesia with hyperbaric bupivacaine in 1 academic institution (2 centers-tertiary and district) from 2012 to 2018. Data were retrieved from the anesthesia information management systems (Metavision, iMDsoft, Tel Aviv, Israel) and the hospital information system, including potential confounding factors, maternal age and weight, hypertensive disease of pregnancy, single/multiple gestation, gestational age, vasopressor administration, planned/urgent surgery, position during anesthesia placement (sitting/lateral), and anesthesiologist seniority. Spinal-induced hypotension was defined as systolic blood pressure that either dropped20% from baseline or100 mm Hg. The primary outcome of interest was the incidence of spinal-induced hypotension according to hyperbaric bupivacaine dose. Logistic regression was used to characterize the association between the dose of hyberbaric bupivacaine and spinal-induced hypotension after adjusting for confounding factors.A total of 8226 women were identified. The hyperbaric bupivacaine dose administered was9 mg for 2395 (29.1%), 9-9.5 mg for 1031 (12.5%), 10 mg for 4155 (50.5%), and10 mg for 645 (7.8%). We used a cutoff (10 vs ≥10 mg) to assess for the primary outcome, using multivariable logistic regression. The incidence of at least 1 spinal-induced hypotension episode was higher in patients who received ≥10 mg hyperbaric bupivacaine, 75.8% vs 62.9% for doses below 10 mg, P.0001; however, even women with lower doses had hypotension. Hyperbaric bupivacaine dose10 mg was associated with a lower incidence of spinal hypotension, adjusted odds ratio (OR) of 0.774, 95% confidence interval (CI), 0.669-0.897, and P = .0006, adjusted for confounding factors.Umbilical cord pH was available for 2684 (32.6%) cases. There were significantly more neonates with pH7.2, among women who received hyperbaric bupivacaine ≥10 mg (10.1%) versus women who received10 mg (6.8%), P = .0032; however, in the adjusted model, hyperbaric bupivacaine dose ≥10 mg was not associated with pH7.2 and an OR of 0.955 (95% CI, 0.631-1.446, P = .829).Our major finding was that hypotension occurred at all doses of hyperbaric bupivacaine, yet occurrence of spinal hypotension was significantly associated with doses ≥10 mg after adjustment for potential confounders.
Published: 2022
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29. Distinct cytokine profiles associated with COVID-19 severity and mortality

Author: Christophe Parizot, Matthieu Schmidt, Hans Yssel, Alexis Mathian, Mehmet Gökkaya, Loïc Le Guennec, Christophe Combadière, Karim Dorgham, Claudia Traidl-Hoffmann, Guillaume Voiriot, Amélie Guihot, Sophie Demeret, Sonia Burrel, Guy Gorochov, Delphine Sauce, Elyes Ben Salah, Paul Quentric, Stéphane Marot, Avidan U. Neumann, Zahir Amoura, Charles-Edouard Luyt, Anne-Geneviève Marcelin, Alexandra Beurton, Béhazine Combadière, Julien Mayaux, Centre d'Immunologie et de Maladies Infectieuses (CIMI), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
Subjects: 0301 basic medicine, Male, principal component analysis, medicine.medical_treatment, SAPS-II, simplified acute physiology score, Gastroenterology, Severity of Illness Index, 0302 clinical medicine, Immunology and Allergy, 030212 general & internal medicine, Respiratory system, Simplified Acute Physiology Score, ComputingMilieux_MISCELLANEOUS, COVID-19, coronavirus disease 2019, TNF, tumor necrosis factor, Covid-19, Mortality, Principal Component Analysis, Respiratory Severity, Serum Cytokines, Type-i Ifns, Middle Aged, ALQ, above upper limit of quantification, 3. Good health, Cytokine, SAPS II, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Cytokines, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Adult, medicine.medical_specialty, Immunology, type-I IFNs, Ag, antigen, serum cytokines, SARS-CoV-2, severe acute respiratory syndrome coronavirus 2, Article, Proinflammatory cytokine, 03 medical and health sciences, Internal medicine, Severity of illness, medicine, Extracorporeal membrane oxygenation, Humans, IFN, interferon, ddc:610, fCC, cytokine combination function, MVS, mechanical ventilatory support, Aged, PCA, principal component analysis, business.industry, SARS-CoV-2, COVID-19, respiratory severity, mortality, Respiration, Artificial, IL, interleukin, 030104 developmental biology, Relative risk, business, ECMO, extracorporeal membrane oxygenation
Abstract: Background Markedly elevated levels of pro-inflammatory cytokines and defective type-I interferon responses were reported in COVID-19 patients. Objective This study aimed to determine whether particular cytokine profiles are associated with COVID-19 severity and mortality. Methods Cytokine concentrations and SARS-CoV-2 antigen were measured at hospital admission in serum of symptomatic COVID-19 patients (N=115), classified at hospitalization into three respiratory severity groups: no need for mechanical ventilatory support (No-MVS), intermediate severity requiring mechanical ventilatory support (MVS) and critical severity requiring extracorporeal membrane oxygenation (ECMO). Principal component analysis was used to characterize cytokine profiles associated with severity and mortality. The results were thereafter confirmed in an independent validation cohort (N=86). Results At time of hospitalization, ECMO patients presented a dominant pro-inflammatory response with elevated levels of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-8 and IL-10. In contrast, an elevated type-I interferon response involving IFN-α and IFN-β was characteristic of No-MVS patients, whereas MVS patients exhibited both profiles. Mortality at one month was associated with higher levels of pro-inflammatory cytokines in ECMO patients, higher levels of type-I interferons in No-MVS patients and their combination in MVS patients, resulting in a combined mortality prediction accuracy of 88.5% (Risk Ratio 24.3, p, Graphical abstract, Capsule SummaryDistinct cytokine profiles are observed in association with COVID-19 severity and are differentially predictive of mortality in different oxygen support modalities. These results warrant personalized treatment of COVID-19 patients based on cytokine profiling.
Published: 2021
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30. Exploring patient perspectives on telemedicine monitoring within the operating room

Author: Alicia Meng, Mary C. Politi, Joanna Abraham, Luke Brawer, Michael S. Avidan, Katherine J. Holzer, and Aparna Casarella
Subjects: Adult, Male, Telemedicine, Operating Rooms, Descriptive statistics, business.industry, Health information technology, Remote patient monitoring, Communication, Health Informatics, Context (language use), medicine.disease, Clinical decision support system, Occupational safety and health, Hospitals, United States, Medicine, Humans, Female, Medical emergency, business, Patient education, Monitoring, Physiologic
Abstract: Clinical decision support systems and telemedicine for remote monitoring can together support clinicians' intraoperative decision-making and management of surgical patients' care. However, there has been limited investigation on patient perspectives about advanced health information technology use in intraoperative settings, especially an electronic OR (eOR) for remote monitoring and management of surgical patients.Our study objectives were: (1) to identify participant-rated items contributing to patient attitudes, beliefs, and level of comfort with eOR monitoring; and (2) to highlight barriers and facilitators to eOR use.We surveyed 324 individuals representing surgical patients across the United States using Amazon Mechanical Turk, an online platform supporting internet-based work. The structured survey questions examined the level of agreement and comfort with eOR for remote patient monitoring. We calculated descriptive statistics for demographic variables and performed a Wilcoxon matched-pairs signed-rank test to assess whether participants were more comfortable with familiar clinicians from local hospitals or health systems monitoring their health and safety status during surgery than clinicians from hospitals or health systems in other regions or countries. We also analyzed open-ended survey responses using a thematic approach informed by an eight-dimensional socio-technical model.Participants' average age was 34.07 (SD = 10.11). Most were white (80.9%), male (57.1%), and had a high school degree or more (88.3%). Participants reported a higher level of comfort with clinicians they knew monitoring their health and safety than clinicians they did not know, even within the same healthcare system (z = -4.012, p .001). They reported significantly higher comfort levels with clinicians within the same hospital or health system in the United States than those in a different country (z = -10.230, p .001). Facilitators and barriers to eOR remote monitoring were prevalent across four socio-technical dimensions: 1) organizational policies, procedures, environment, and culture; 2) people; 3) workflow and communication; and 4) hardware and software. Facilitators to eOR use included perceptions of improved patient safety through a safeguard system and perceptions of streamlined care. Barriers included fears of incorrect eOR patient assessments, decision-making conflicts between care teams, and technological malfunctions.Participants expressed significant support for intraoperative telemedicine use and greater comfort with local telemedicine systems instead of long-distance telemedicine systems. Reservations centered on organizational policies, procedures, environment, culture; people; workflow and communication; and hardware and software. To improve the buy-in and acceptability of remote monitoring by an eOR team, we offer a few evidence-based guidelines applicable to telemedicine use within the context of OR workflow. Guidelines include backup plans for technical challenges, rigid care, and privacy standards, and patient education to increase understanding of telemedicine's potential to improve patient care.
Published: 2021

31. Recovery of consciousness and cognition after general anesthesia in humans

Author: Hannah R. Maybrier, Michael S. Avidan, Randall Hardie, Mathias Basner, Giancarlo Vanini, Duan Li, Goodarz Golmirzaie, Vijay Tarnal, Ben Ja Palanca, Kaitlyn Maier, George A. Mashour, Marlon Schwartz, Andrew R. McKinstry-Wu, Max B. Kelz, Maxwell R. Muench, Wei Wang, Rosemary Hogg, Nan Lin, E. Andrew Ochroch, Ellen Janke, Stefanie Blain-Moraes, and Paul Picton
Subjects: Male, cognition, Brain activity and meditation, Unconsciousness, Electroencephalography, consciousness, 0302 clinical medicine, 030202 anesthesiology, Medicine, Biology (General), media_common, Isoflurane, medicine.diagnostic_test, frontal cortex, General Neuroscience, Brain, Cognition, General Medicine, Human brain, medicine.anatomical_structure, Anesthesia, Female, medicine.symptom, Research Article, Human, medicine.drug, Adult, QH301-705.5, media_common.quotation_subject, Science, Anesthesia, General, anesthesia, General Biochemistry, Genetics and Molecular Biology, Arousal, 03 medical and health sciences, Humans, Coma, General Immunology and Microbiology, Working memory, business.industry, Actigraphy, Anesthesia Recovery Period, Neurocognitive Tests, Anesthetic, Delirium, Consciousness, business, 030217 neurology & neurosurgery, Neuroscience
Abstract: Understanding how the brain recovers from unconsciousness can inform neurobiological theories of consciousness and guide clinical investigation. To address this question, we conducted a multicenter study of 60 healthy humans, half of whom received general anesthesia for 3 hr and half of whom served as awake controls. We administered a battery of neurocognitive tests and recorded electroencephalography to assess cortical dynamics. We hypothesized that recovery of consciousness and cognition is an extended process, with differential recovery of cognitive functions that would commence with return of responsiveness and end with return of executive function, mediated by prefrontal cortex. We found that, just prior to the recovery of consciousness, frontal-parietal dynamics returned to baseline. Consistent with our hypothesis, cognitive reconstitution after anesthesia evolved over time. Contrary to our hypothesis, executive function returned first. Early engagement of prefrontal cortex in recovery of consciousness and cognition is consistent with global neuronal workspace theory., eLife digest Anesthesia is a state of reversable, controlled unconsciousness. It has enabled countless medical procedures. But it also serves as a tool for scientists to study how the brain regains consciousness after disruptions such as sleep, coma or medical procedures requiring general anesthesia. It is still unclear how exactly the brain regains consciousness, and less so, why some patients do not recover normally after general anesthesia or fail to recover from brain injury. To find out more, Mashour et al. studied the patterns of reemerging consciousness and cognitive function in 30 healthy adults who underwent general anesthesia for three hours. While the volunteers were under anesthesia, their brain activity was measured with an EEG; and their sleep-wake activity was measured before and after the experiment. Each participant took part in a series of cognitive tests designed to measure the reaction speed, memory and other functions before receiving anesthesia, right after the return of consciousness, and then every 30 minutes thereafter. Thirty healthy volunteers who did not have anesthesia also completed the scans and tests as a comparison group. The experiments showed that certain normal EEG patterns resumed just before a person wakes up from anesthesia. The return of thinking abilities was an extended, multistep process, but volunteers recovered their cognitive abilities to nearly the same level as the volunteers within three hours of being deeply anesthetized. Mashour et al. also unexpectedly found that abstract problem-solving resumes early in the process, while other functions such as reaction time and attention took longer to recover. This makes sense from an evolutionary perspective. Sleep leaves individuals vulnerable. Quick evaluation and decision-making skills would be key to respond to a threat upon waking. The experiments confirm that the front of the brain, which handles thinking and decision-making, was especially active around the time of recovery. This suggests that therapies targeting this part of the brain may help people who experience loss of consciousness after a brain injury or have difficulties waking up after anesthesia. Moreover, disorders of cognition, such as delirium, in the days following surgery may be caused by factors other than the lingering effects of anesthetic drugs on the brain.
Published: 2021

32. Use of Machine Learning to Develop and Evaluate Models Using Preoperative and Intraoperative Data to Identify Risks of Postoperative Complications

Author: Bing Xue, Troy S. Wildes, Thomas George Kannampallil, Dingwen Li, Michael S. Avidan, Christopher R. King, Chenyang Lu, and Joanna Abraham
Subjects: Male, Deep vein, Machine learning, computer.software_genre, Logistic regression, Preoperative care, Risk Assessment, Machine Learning, Intraoperative Period, Postoperative Complications, Risk Factors, medicine, Humans, Retrospective Studies, Receiver operating characteristic, business.industry, Incidence, Retrospective cohort study, General Medicine, Perioperative, Middle Aged, medicine.disease, Decision Support Systems, Clinical, United States, Pulmonary embolism, medicine.anatomical_structure, ROC Curve, Preoperative Period, Delirium, Female, Artificial intelligence, medicine.symptom, business, computer, Follow-Up Studies
Abstract: Importance Postoperative complications can significantly impact perioperative care management and planning. Objectives To assess machine learning (ML) models for predicting postoperative complications using independent and combined preoperative and intraoperative data and their clinically meaningful model-agnostic interpretations. Design, setting, and participants This retrospective cohort study assessed 111 888 operations performed on adults at a single academic medical center from June 1, 2012, to August 31, 2016, with a mean duration of follow-up based on the length of postoperative hospital stay less than 7 days. Data analysis was performed from February 1 to September 31, 2020. Main outcomes and measures Outcomes included 5 postoperative complications: acute kidney injury (AKI), delirium, deep vein thrombosis (DVT), pulmonary embolism (PE), and pneumonia. Patient and clinical characteristics available preoperatively, intraoperatively, and a combination of both were used as inputs for 5 candidate ML models: logistic regression, support vector machine, random forest, gradient boosting tree (GBT), and deep neural network (DNN). Model performance was compared using the area under the receiver operating characteristic curve (AUROC). Model interpretations were generated using Shapley Additive Explanations by transforming model features into clinical variables and representing them as patient-specific visualizations. Results A total of 111 888 patients (mean [SD] age, 54.4 [16.8] years; 56 915 [50.9%] female; 82 533 [73.8%] White) were included in this study. The best-performing model for each complication combined the preoperative and intraoperative data with the following AUROCs: pneumonia (GBT), 0.905 (95% CI, 0.903-0.907); AKI (GBT), 0.848 (95% CI, 0.846-0.851); DVT (GBT), 0.881 (95% CI, 0.878-0.884); PE (DNN), 0.831 (95% CI, 0.824-0.839); and delirium (GBT), 0.762 (95% CI, 0.759-0.765). Performance of models that used only preoperative data or only intraoperative data was marginally lower than that of models that used combined data. When adding variables with missing data as input, AUROCs increased from 0.588 to 0.905 for pneumonia, 0.579 to 0.848 for AKI, 0.574 to 0.881 for DVT, 0.5 to 0.831 for PE, and 0.6 to 0.762 for delirium. The Shapley Additive Explanations analysis generated model-agnostic interpretation that illustrated significant clinical contributors associated with risks of postoperative complications. Conclusions and relevance The ML models for predicting postoperative complications with model-agnostic interpretation offer opportunities for integrating risk predictions for clinical decision support. Such real-time clinical decision support can mitigate patient risks and help in anticipatory management for perioperative contingency planning.
Published: 2021

33. Differential classification of states of consciousness using envelope- and phase-based functional connectivity

Author: Vijay Tarnal, Giancarlo Vanini, Goodarz Golmirzaie, Yacine Mahdid, Max B. Kelz, George A. Mashour, Paul Picton, Michael S. Avidan, Lucrezia Liuzzi, Charlotte Maschke, Ellen Janke, Jason Da Silva Castanheira, Kathleen Berkun, Stefanie Blain-Moraes, Catherine Duclos, and Matthew J. Brookes
Subjects: Adult, Male, medicine.medical_specialty, Support Vector Machine, Consciousness, Cognitive Neuroscience, Sedation, media_common.quotation_subject, Electroencephalography Phase Synchronization, Network, Neurosciences. Biological psychiatry. Neuropsychiatry, Unconsciousness, Audiology, Electroencephalography, 050105 experimental psychology, Correlation, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Machine learning, medicine, Connectome, Humans, 0501 psychology and cognitive sciences, Anesthesia, media_common, Cerebral Cortex, Connectivity, medicine.diagnostic_test, business.industry, 05 social sciences, Neurology, Anesthetic, Female, medicine.symptom, Nerve Net, Propofol, business, 030217 neurology & neurosurgery, RC321-571, medicine.drug, Envelope (motion)
Abstract: The development of sophisticated computational tools to quantify changes in the brain's oscillatory dynamics across states of consciousness have included both envelope- and phase-based measures of functional connectivity (FC), but there are very few direct comparisons of these techniques using the same dataset. The goal of this study was to compare an envelope-based (i.e. Amplitude Envelope Correlation, AEC) and a phase-based (i.e. weighted Phase Lag Index, wPLI) measure of FC in their classification of states of consciousness. Nine healthy participants underwent a three-hour experimental anesthetic protocol with propofol induction and isoflurane maintenance, in which five minutes of 128-channel electroencephalography were recorded before, during, and after anesthetic-induced unconsciousness, at the following time points: Baseline; light sedation with propofol (Light Sedation); deep unconsciousness following three hours of surgical levels of anesthesia with isoflurane (Unconscious); five minutes prior to the recovery of consciousness (Pre-ROC); and three hours following the recovery of consciousness (Recovery). Support vector machine classification was applied to the source-localized EEG in the alpha (8–13 Hz) frequency band in order to investigate the ability of AEC and wPLI (separately and together) to discriminate i) the four states from Baseline; ii) Unconscious (“deep” unconsciousness) vs. Pre-ROC (“light” unconsciousness); and iii) responsiveness (Baseline, Light Sedation, Recovery) vs. unresponsiveness (Unconscious, Pre-ROC). AEC and wPLI yielded different patterns of global connectivity across states of consciousness, with AEC showing the strongest network connectivity during the Unconscious epoch, and wPLI showing the strongest connectivity during full consciousness (i.e., Baseline and Recovery). Both measures also demonstrated differential predictive contributions across participants and used different brain regions for classification. AEC showed higher classification accuracy overall, particularly for distinguishing anesthetic-induced unconsciousness from Baseline (83.7 ± 0.8%). AEC also showed stronger classification accuracy than wPLI when distinguishing Unconscious from Pre-ROC (i.e., “deep” from “light” unconsciousness) (AEC: 66.3 ± 1.2%; wPLI: 56.2 ± 1.3%), and when distinguishing between responsiveness and unresponsiveness (AEC: 76.0 ± 1.3%; wPLI: 63.6 ± 1.8%). Classification accuracy was not improved compared to AEC when both AEC and wPLI were combined. This analysis of source-localized EEG data demonstrates that envelope- and phase-based FC provide different information about states of consciousness but that, on a group level, AEC is better able to detect relative alterations in brain FC across levels of anesthetic-induced unconsciousness compared to wPLI.
Published: 2021

34. Effect of acute postsurgical pain trajectories on 30-day and 1-year pain

Author: Saria S. Awadalla, Victoria Winslow, Michael S. Avidan, Simon Haroutounian, and Thomas G. Kannampallil
Subjects: Adult, Cohort Studies, Male, Pain, Postoperative, Multidisciplinary, Quality of Life, Humans, Female, Middle Aged, Acute Pain, Pain Measurement
Abstract: Untreated pain after surgery leads to poor patient satisfaction, longer hospital length of stay, lower health-related quality of life, and non-compliance with rehabilitation regimens. The aim of this study is to characterize the structure of acute pain trajectories during the postsurgical hospitalization period and quantify their association with pain at 30-days and 1-year after surgery. This cohort study included 2106 adult (≥18 years) surgical patients who consented to participate in the SATISFY-SOS registry (February 1, 2015 to September 30, 2017). Patients were excluded if they did not undergo invasive surgeries, were classified as outpatients, failed to complete follow up assessments at 30-days and 1-year following surgery, had greater than 4-days of inpatient stay, and/or recorded fewer than four pain scores during their acute hospitalization period. The primary exposure was the acute postsurgical pain trajectories identified by a machine learning-based latent class approach using patient-reported pain scores. Clinically meaningful pain (≥3 on a 0–10 scale) at 30-days and 1-year after surgery were the primary and secondary outcomes, respectively. Of the study participants (N = 2106), 59% were female, 91% were non-Hispanic White, and the mean (SD) age was 62 (13) years; 41% of patients underwent orthopedic surgery and 88% received general anesthesia. Four acute pain trajectory clusters were identified. Pain trajectories were significantly associated with clinically meaningful pain at 30-days (p = 0.007), but not at 1-year (p = 0.79) after surgery using covariate-adjusted logistic regression models. Compared to Cluster 1, the other clusters had lower statistically significant odds of having pain at 30-days after surgery (Cluster 2: [OR = 0.67, 95%CI (0.51–0.89)]; Cluster 3:[OR = 0.74, 95%CI (0.56–0.99)]; Cluster 4:[OR = 0.46, 95%CI (0.26–0.82)], all p
Published: 2022
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35. Use of failure-to-rescue to identify international variation in postoperative care in low-, middle- and high-income countries

Author: Ahmad T., Bouwman R. A., Grigoras I., Aldecoa C., Hofer C., Hoeft A., Holt P., Buhre W., Pearse R. M., Clavien P. -A., Demartines N., Grocott M., Haddow J., Moreno R., Pritchard N., Rhodes A., Wilson M., Ahmed T., Halliwell R., Shulman M., Myles P., Schmid W., Hiesmayr M., Wouters P., De Hert S., Lobo S., Beattie S., Wijeysundera D., Fang X., Rasmussen L., Futier E., Biais M., Venara A., Slim K., Sander M., Koulenti D., Arvaniti K., Chan M., Kulkarni A., Chandra S., Tantri A., Geddoa E., Abbas M., Della Rocca G., Sivasakthi D., Mansor M., Luna P., Bouwman A., Beavis V., Campbell D., Short T., Osinaike T., Matos R., Kirov M., Protsenko D., Biccard B., Chew M., Hubner M., Ditai J., Szakmany T., Fleisher L., Ferguson M., MacMahon M., Cherian R., Currow H., Kanathiban K., Gillespie D., Pathmanathan E., Phillips K., Reynolds J., Rowley J., Douglas J., Kerridge R., Garg S., Bennett M., Jain M., Alcock D., Terblanche N., Cotter R., Leslie K., Stewart M., Zingerle N., Clyde A., Hambidge O., Rehak A., Cotterell S., Huynh W. B. Q., McCulloch T., Ben-Menachem E., Egan T., Cope J., Fellinger P., Markus P., Haselberger S., Holaubek C., Lichtenegger P., Scherz F., Hoffer F., Cakova V., Eichwalder A., Fischbach N., Klug R., Schneider E., Vesely M., Wickenhauser R., Gernot K., Leitgeb M., Lang F., Toro N., Bauer M., Laengle F., Haberl C., Mayrhofer T., Trybus C., Buerkle C., Forstner K., Germann R., Rinoesl H., Schindler E., Trampitsch E., Bogner G., Dankl D., Duenser M., Fritsch G., Gradwohl I. -M., Hartmann A., Hoelzenbein T., Jaeger T., Landauer F., Lindl G., Lux M., Steindl J., Stundner O., Szabo C., Bidgoli J., Verdoodt H., Forget P., Kahn D., Lois F., Momeni M., Pregardien C., Pospiech A., Steyaert A., Veevaete L., De Kegel D., De Jongh K., Foubert L., Smitz C., Vercauteren M., Poelaert J., Van Mossevelde V., Abeloos J., Bouchez S., Coppens M., De Baerdemaeker L., Deblaere I., De Bruyne A., Fonck K., Heyse B., Jacobs T., Lapage K., Moerman A., Neckebroek M., Parashchanka A., Roels N., Van Den Eynde N., Vandenheuvel M., Van Limmen J., Vanluchene A., Vanpeteghem C., Wyffels P., Huygens C., Vandenbempt P., Van De Velde M., Dylst D., Janssen B., Schreurs E., Aleixo F. B., Candido K., Batista H. D., Guimaraes M., Guizeline J., Hoffmann J., Lobo F. R. M., Nascimento V., Nishiyama K., Pazetto L., Souza D., Rodrigues R. S., Dos Santos A. M. V., Jardim J., Sa Malbouisson L. M., Silva J., Do Nascimento P., Baio T. H., De Castro G. I. P., Oliveira H. R. W., Amendola C. P., Cardoso G., Ortega D., Brotto A. F., De Oliveira M. C., Rea-Neto A., Dias F., Travi M. E., Zerman L., Azambuja P., Knibel M. F., Martins A., Almeida W., Neto C. N., Tardelli M. A., Caser E., MacHado M., Aguzzoli C., Baldisserotto S., Tabajara F. B., Bettega F., Rodrigues L. H. C., De Gasperi J., Faina L., Nolasco M. F., Da Costa Fischer B. F., De Campos Ferreira M. F., Hartmann C., Kliemann M., Ribeiro G. L. H., Fraga J. M., Netto T. M., Pozza L. V., Wendling P. R., Azevedo C., Garcia J., Lopes M., Maia B., Maselli P., Melo R., Mendes W., Neves M., Ney J., Piras C., Applewhaite C., Carr A., Chow L., Duttchen K., Foglia J., Greene M., Hinther A., Houston K., McCormick T. J., Mikhayel J., Montasser S., Ragan A., Suen A., Woolsey A., Yu H. C., Funk D., Stephen D., Regina D., Heather D., Faisal D., Pridham J., Rowe B., Sampson S., Thiessen B., Zbitnew G., Bernard A., George R., Jones P., Moor R., Siddiqui N., Wolfer A., Tran D., Winch D., Dobson G., Montasser O., Hall R., Baghirzada L., Curley G., Dai S. Y., Hare G., Lee E., Shastri U., Tsui A., Yagnik A., Alvares D., Choi S., Dwyer H., Flores K., McCartney C., Somascanthan P., Carroll J., Pazmino-Canizares J., Ami N., Chan V., Perlas A., Argue R., Huang Y., Lavis K., Mayson K., Cao Y., Gao H., Hu T., Lv J., Yang J., Yang Y., Zhong Y., Zhou J., Zou X., He M., Li X., Luo D., Wang H., Yu T., Chen L., Wang L., Cai Y., Cao Z., Li Y., Lian J., Sun H., Wang S., Wang Z., Wang K., Zhu Y., Du X., Fan H., Fu Y., Huang L., Hwan H., Luo H., Qu P. -S., Tao F., Wang G., Zhang Y., Zhang X., Chen C., Wang W., Liu Z., Fan L., Tang J., Chen Y., Han Y., Huang C., Liang G., Shen J., Wang J., Yang Q., Zhen J., Zhou H., Chen J., Chen Z., Meng B., Ye H., Bi Y., Cao J., Guo F., Lin H., Liu Y., Lv M., Shi P., Song X., Sun C., Sun Y., Wang Y., Zhang M., Chen R., Hou J., Leng Y., Meng Q. -T., Qian L., Shen Z. -Y., Xia Z. -Y., Xue R., Zhao B., Zhou X. -J., Chen Q., Guo H., Guo Y., Qi Y., Wei J., Zhang W., Zheng L., Bao Q., Fei Y., Hu N., Hu X., Lei M., Lv X., Miao F., Ouyang L., Shen C., Wang D., Wu C., Xu L., Yuan J., Zhang L., Zhang H., Zhao J., Zhao C., Zhao L., Zheng T., Zhou D., Zhou C., Lu K., Zhao T., He C., Chen H., Chen S., Cheng B., He J., Jin L., Li C., Li H., Pan Y., Shi Y., Wen X. H., Wu S., Xie G., Zhang K., Lu X., Chen F., Liang Q., Lin X., Ling Y., Liu G., Tao J., Yang L., Cheng Z., Dai H., Feng Y., Hou B., Gong H., Hua C., Huang H., Huang J., Jiang Z., Li M., Lin J., Liu M., Liu W., Luo F., Ma L., Min J., Shi X., Song Z., Wan X., Xiong Y., Yang S., Zhang Q., Zhao W., Zhu X., Bai Y., Dai Q., Geng W., Han K., He X., Ji B., Jia D., Jin S., Li Q., Liang D., Luo S., Lwang L., Mo Y., Qi X., Qian M., Qin J., Ren Y., Xie J., Yan Y., Yao Y., Zhuang X., Ai Y., Du F., He L., Li Z., Li L., Meng S., Yuan Y., Zhang E., Zhang J., Zhao S., Ji Z., Pei L., Dong B., Li J., Miao Z., Mu H., Qin C., Su L., Wen Z., Xie K., Yu Y., Yuan F., Xiao W., Zhu Z., Fu K., Hu R., Huang S., Liang Y., Yu S., Guo Z., Jing Y., Tang N., Wu J., Yuan D., Zhang R., Zhao X., Bai H. -P., Liu C. -X., Liu F. -F., Ren W., Wang X. -L., Xu G. -J., Li B., Ou Y., Tang Y., Yao S., Zhang S., Kong C. -C., Liu B., Wang T., Lu B., Xia Y., Cai F., Chen P., Hu S., Xu Q., Hu L., Jing L., Liu Q., Dan Z., Qiu X., Ren Q., Tong Y., Wen Y., Wu Q., Xia J., Xiong X., Xu S., Yang T., Yin N., Zeng Q., Zhang B., Zheng K., Cang J., Fan Y., Fu S., Ge X., Guo B., Huang W., Jiang L., Jiang X., Shan Q., Wang F., Christiansen I. C., Granum S. N., Rasmussen B. S., Daugaard M., Gambhir R., Brandsborg B., Steingrimsdottir G. E., Jensen-Gadegaard P., Kovgaard K. O., Siegel H., Eskildsen K. Z., Gatke M. R., Wibrandt I., Heintzelmann S. B., Lange K. H. W., Lundsgaard R. S., Amstrup-Hansen L., Hovendal C., Larsen M., Lenstrup M., Kobborg T., Larsen J. R., Pedersen A. B., Smith S. H., Oestervig R. M., Afshari A., Andersen C., Ekelund K., Lilja E., Beloeil H., Lasocki S., Ouattara A., Sineus M., Molliex S., Legouge M. L., Wallet F., Tesniere A., Gaudin C., Lehur P., Forsans E., De Rudnicki S., Maudet V. S., Sojod G., Ouaissi M., Regimbeau J. -M., Desbordes J., Comptaer N., El Manser D., Ethgen S., Lebuffe G., Auer P., Hartl C., Deja M., Legashov K., Sonnemann S., Wiegand-Loehnert C., Falk E., Habicher M., Angermair S., Laetsch B., Schmidt K., Von Heymann C., Ramminger A., Jelschen F., Pabel S., Weyland A., Czeslick E., Gille J., Malcharek M., Sablotzki A., Lueke K., Wetzel P., Weimann J., Lenhart F. -P., Reichle F., Schirmer F., Huppe M., Klotz K., Nau C., Schon J., Mencke T., Wasmund C., Bankewitz C., Baumgarten G., Fleischer A., Guttenthaler V., Hack Y., Kirchgaessner K., Manner O., Schurig-Urbaniak M., Struck R., Van Rebekkazyl, Wittmann M., Goebel U., Harris S., Veit S., Andreadaki E., Souri F., Katsiadramis I., Skoufi A., Vasileiou M., Aimoniotou-Georgiou E., Katsourakis A., Veroniki F., Vlachogianni G., Petra K., Chlorou D., Oloktsidou E., Ourailoglou V., Papapostolou K., Tsaousi G., Daikou P., Dedemadi G., Kalaitzopoulos I., Loumpias C., Bristogiannis S., Dafnios N., Gkiokas G., Kontis E., Kozompoli D., Papailia A., Theodosopoulos T., Bizios C., Koutsikou A., Moustaka A., Plaitakis I., Armaganidis A., Christodoulopoulou T., Lignos M., Theodorakopoulou M., Asimakos A., Ischaki E., Tsagkaraki A., Zakynthinos S., Antoniadou E., Koutelidakis I., Lathyris D., Pozidou I., Voloudakis N., Dalamagka M., Elena G., Chronis C., Manolakaki D., Mosxogiannidis D., Slepova T., Tsakiridou I. -S., Lampiri C., Vachlioti A., Panagiotakis C., Sfyras D., Tsimpoukas F., Tsirogianni A., Axioti E., Filippopoulos A., Kalliafa E., Kassavetis G., Katralis P., Komnos I., Pilichos G., Ravani I., Totis A., Apagaki E., Efthymiadi A., Kampagiannis N., Paraforou T., Tsioka A., Georgiou G., Vakalos A., Bairaktari A., Charitos E., Markou G., Niforopoulou P., Papakonstantinou N., Tsigou E., Xifara A., Zoulamoglou M., Gkioni P., Karatzas S., Kyparissi A., Mainas E., Papapanagiotou I., Papavasilopoulou T., Fragandreas G., Georgopoulou E., Katsika E., Psarras K., Synekidou E., Verroiotou M., Vetsiou E., Zaimi D., Anagnou A., Apostolou K., Melissopoulou T., Rozenberg T., Tsigris C., Boutsikos G., Kalles V., Kotsalas N., Lavdaiou C., Paikou F., Panagou G. -L., Spring A., Botis I., Drimala M., Georgakakis G., Kiourtzieva E., Ntouma P., Prionas A., Xouplidis K., Dalampini E., Giannaki C., Iasonidou C., Ioannidis O., Lavrentieva A., Papageorgiou G., Kokkinoy M., Stafylaraki M., Gaitanakis S., Karydakis P., Paltoglou J., Ponireas P., Chaloulis P., Provatidis A., Sousana A., Gardikou V. V., Konstantivelli M., Lataniotou O., Lisari E., Margaroni M., Stamatiou K., Nikolaidis E., Pnevmatikos I., Sertaridou E., Andreou A., Arkalaki E., Athanasakis E., Chaniotaki F., Chatzimichali C. A., Christofaki M., Dermitzaki D., Fiorentza K., Frantzeskos G., Geromarkaki E., Kafkalaki K., Kalogridaki M., Karydi K., Kokkini S., Kougentakis G., Lefaki T., Lilitsis E., Makatounaki A., Malliotakis P., Michelakis D., Neonaki M., Nyktari V., Palikyra I., Papadakis E., Papaioannou A., Sfakianakis K., Sgouraki M., Souvatzis X., Spartinou A., Stefanidou N., Syrogianni P., Tsagkaraki G., Arnaoutoglou E., Arnaoutoglou C., Bali C., Bouris V., Doumos R., Gkini K. -P., Kapaktsi C., Koulouras V., Lena A., Lepida D., Michos E., Papadopoulos D., Paschopoulos M., Rompou V. A., Siouti I., Tsampalas S., Ververidou O., Zilis G., Charlalampidoy A., Christodoulidis G., Flossos A., Stamoulis K., Tsang M. S. C., Lai M. L., Yip C. P., Chan H. M. H., Law B., Li W. S., Chu H. M., Koo E. G. Y., Lam C. C. J., Cheng K. H., Lam T., Chu S., Lam W. Y., Wong K. W. K., Kwok D., Hung C. Y. J., Chan W. K. J., Wong W. L., Chung C. K. E., Ma S. K., Kaushik S., Shah B., Shah D., Shah S., Ar P., Muthuchellappan R., Agarwal V., Divatia J., Mishra S., Nimje G., Pande S., Savarkar S., Shrivastava A., Thomas M., Yegnaram S., Hidayatullah R., Puar N., Niman S., Indra I., Hamzah Z., Yuliana A., Abidin U. N., Dursin A. N., Kurnia A., Susanti A., Handayani D., Alit M. A., Arya A., Senapathi T. G. A., Utara U. H., Wid W. M., Wima S., Wir W. M., Jehosua B., Kaunang J., Lantang E. Y., Najoan R., Waworuntu N., Awad H., Fuad A., Geddoa B., Khalaf A. R., Al Hussaini S., Albaj S., Kenber M., Bettinelli A., Spadaro S., AlbertoVolta C., Giancarlo L., Sottosanti V., Copetti U. E., Spagnesi L., Toretti I., Alloj C., Cardellino S., Carmino L., Costanzo E., Fanfani L. C., Novelli M. T., Roasio A., Bellandi M. M., Beretta L., Bignami E., Bocchino S., Cabrini L., Corti D., Landoni G., Meroni R., Moizo E., Monti G., Pintaudi M., Plumari V. P., Taddeo D., Testa V., Winterton D., Zangrillo A., Cloro R. L. M., Colangelo C., Colangelo A., Rotunno G., Paludi M. A., Maria C. P., Pata A., Parrini V., Gatta A., Nastasi M., Tinti C., Baroselli A., Arrigo M., Benevento A., Bottini C., Cannavo M., Gastaldi C., Marchesi A., Pascazio A., Pata F., Pozzi E., Premoli A., Tessera G., Boschi L., D'Andrea R., Ghignone F., Poggioli G., Sibilio A., Taffurelli M., Ugolini G., Ab Majid M. A., Ab Rahman R., Joseph J., Pathan F., Shah M. H. S., Yap H. L., Cheah S., Chin I. I., Looi J. K., Tan S. C., Visvalingam S., Kwok F. Y., Lee C. K., Tan T. S., Wong S. M., Abdullah N. H., Liew C. F., Luxuman L., Mohd Zin N. H., Norddin M. F., Alias R. L. R., Wong J. Y., Yong J., Mustapha M. T. B., Chan W. K., Dzulkipli N., Kuan P. X., Lee Y. C., Alias A., Guok E. C., Jee C. C., Ramon B. R., Wong C. W., Abd Ghafar F. N. I., Aziz F. Z., Hussain N., Lee H. S., Sukawi I., Woon Y. L., Abd Hadi H. Z., Azam U. A. A., Alias A. H., Kesut S. A., Lee J. M., Ooi D. V., Sulaiman H. A., Lih T. A. T., Veerakumaran J., Rojas E., Resendiz G. E. A., Zapata D. D. M., Lopez J. C. J. A., Flores A. A. A., Amador J. C. B., Avila E. J. D., Aquino L. P. G., Rodriguez R. L., Landa M. T., Urias E., Hollmann M., Hulst A., Preckel O. K. B., Gemert A. K. -V., Buise M., Tolenaar N., Weber E., De Fretes J., Houweling P., Ormskerk P., Van Bommel J., Lance M., Smit-Fun V., Van Zundert T., Baas P., De Boer H. D., Sprakel J., Elferink-Vonk R., Noordzij P., Van Zeggeren L., Brand B., Spanjersberg R., Ten Bokkel-Andela J., Numan S., Van Klei W., Van Zaane B., Boer C., Van Duivenvoorde Y., Hering J. P., Van Rossum S., Zonneveldt H., Hoare S., Santa S., Ali M., Allen S. J., Bell R., Choi H. -M. D., Drake M., Farrell H., Hayes K., Higgie K., Holmes K., Jenkins N., Kim C. J., Kim S., Law K. C., McAllister D., Park K., Pedersen K., Pfeifer L., Pozaroszczyk A., Salmond T., Steynor M., Tan M., Waymouth E., Ab Rahman A. S., Armstrong J., Dudson R., Nilakant J., Richard S., Virdi P., Dixon L., Donohue R., Farrow M., Kennedy R., Marissa H., McKellow M., Nicola D., Pascoe R., Roberts S. J., Rowell G., Sumner M., Templer P., Chandrasekharan S., Fulton G., Jammer I., More R., Wilson L., Hsuan Y., Foley J., Fowler C., Panckhurst J., Sara R., Stapelberg F., Cherrett V., Ganter D. L., McCann L., Gilmour F., Lumsden R., Moores M., Olliff S., Sardareva E., Tai J., Wikner M., Wong C., Chaddock M., Czepanski C., McKendry P., Polakovic D., Polakovich D., Robert A., Belda M. T., Norton T., Alherz F., Barneto L., Ramirez A., Sayeed A., Smith N., Bennett C., McQuoid S., Jansen T. -L., Nico Z., Scott J., Freschini D., Freschini A., Hopkins B., Manson L., Stoltz D., Bates A., Davis S., Freeman V., McGaughran L., Williams M., Sharma S. B., Burrows T., Byrne K., English D., Johnson R., Manikkam B., Naidoo S., Rumball M., Whittle N., Franks R., Gibson-Lapsley H., Salter R., Walsh D., Richard D., Perry K., Obobolo A., Sule U. M., Ahmad A., Atiku M., Mohammed A. D., Sarki A. M., Adekola O., Akanmu O., Durodola A., Olukoju O., Raji V., Olajumoke T., Oyebamiji E., Adenekan A., Adetoye A., Faponle F., Olateju S., Owojuyigbe A., Talabi A., Adenike O., Adewale B., Collins N., Ezekiel E., Fatungase O. M., Grace A., Sola S., Stella O., Ademola A., Adeolu A. A., Adigun T., Akinwale M., Fasina O., Gbolahan O., Idowu O., Olonisakin R. P., Osinaike B. B., Asudo F., Mshelia D., Abdur-Rahman L., Agodirin O., Bello J., Bolaji B., Oyedepo O. O., Ezike H., Iloabachie I., Okonkwo I., Onuora E., Onyeka T., Ugwu I., Umeh F., Alagbe-Briggs O., Dodiyi-Manuel A., Echem R., Obasuyi B., Onajin-Obembe B., Bandeira M. E., Tome M., Costa A. C. M. M., Krystopchuk A., Branco T., Esteves S., Melo M. A., Monte J., Rua F., Martins I., Pinho-Oliveira V. M., Rodrigues C. M., Cabral R., Marques S., Rego S., Jesus J. S. T., Marques M. C., Romao C., Dias S., Santos A. M., Alves M. J., Salta C., Cruz S., Duarte C., Paiva A. A. F., Do Nascimento Cabral T., E Maia D. F., Da Silva R. F. M. C., Langner A., Resendes H. O., Da Conceicao Soares M., Abrunhosa A., Faria F., Miranda L., Pereira H., Serra S., Ionescu D., Margarit S., Mitre C., Vasian H., Manga G., Stefan A., Tomescu D., Daniela D., Paunescu M. -A., Stefan M., Stoica R., Gavril L., Patrascanu E., Ristescu I., Rusu D., Diaconescu C., Iosep G. F., Pulbere D., Ursu I., Balanescu A., Grintescu I., Mirea L., Rentea I., Vartic M., Lupu M. -N., Stanescu D., Streanga L., Antal O., Hagau N., Patras D., Petrisor C., Tosa F., Tranca S., Copotoiu S. M., Ungureanu L. L., Harsan C. R., Papurica M., Cernea D. D., Dragoescu N. A., Aflori L., Vaida C., Ciobotaru O. R., Aignatoaie M., Carp C. P., Cobzaru I., Mardare O., Purcarin B., Tutunaru V., Ionita V., Arustei M., Codita A., Busuioc M., Chilinciuc I., Ciobanu C., Belciu I., Tincu E., Blaj M., Grosu R. -M., Sandu G., Bruma D., Corneci D., Dutu M., Krepil A., Copaciu E., Dumitrascu C. O., Jemna R., Mihaescu F., Petre R., Tudor C., Ursache E., Kulikov A., Lubnin A., Grigoryev E., Pugachev S., Tolmasov A., Hussain A., Ilyina Y., Roshchina A., Iurin A., Chazova E., Dunay A., Karelov A., Khvedelidze I., Voldaeva O., Belskiy V., Dzhamullaev P., Grishkowez E., Kretov V., Levin V., Molkov A., Puzanov S., Samoilenko A., Tchekulaev A., Tulupova V., Utkin I., Allorto N. L., Bishop D. G., Builu P. M., Cairns C., Dasrath A., De Wet J., Den Hoedt M., Grey B., Hayes M. P., Kusel B. S., Shangase N., Wise R., Cacala S., Farina Z., Govindasamy V., Kruse C. -H., Lee C., Marais L., Naidoo T. D., Rajah C., Rodseth R. N., Ryan L., Von Rhaden R., Adam S., Alphonsus C., Ameer Y., Anderson F., Basanth S., Bechan S., Bhula C., Biccard B. M., Biyase T., Buccimazza I., Cardosa J., Daya B., Drummond L., Elabib A., Goad E. H. A., Goga I. E., Goga R., Harrichandparsad R., Hodgson R. E., Jordaan J., Kalafatis N., Kampik C., Landers A. T., Loots E., Madansein R., Madaree A., Madiba T. E., Manzini V. T., Mbuyisa M., Moodley R., Msomi M., Mukama I., Naidoo D., Naidoo R., Naidu T. K., Ntloko S., Padayachee E., Padayachee L., Phaff M., Pillay B., Pillay D., Pillay L., Ramnarain A., Ramphal S. R., Ryan P., Saloojee A., Sebitloane M., Sigcu N., Taylor J. L., Torborg A., Visser L., Anderson P., Conradie A., De Swardt M., De Villiers M., Eikman J., Liebenberg R., Mouton J., Paton A., Van Der Merwe L., Wilscott-Davids C., Barrett W. J., Bester M., De Beer J., Geldenhuys J., Gouws H., Potgieter J. -H., Strydom M., Turton E. W., Chetty R. R., Chirkut S., Cronje L., De Vasconcellos K., Dube N. Z., Gama N. S., Green G. M., Green-Thompson R., Kinoo S. M., Kistnasami P., Maharaj K., Moodley M. S., Mothae S. J., Noorbhai M. A. F., Rughubar V., Reddy J., Singh A., Skinner D. L., Smith M. J., Singh B., Misra R., Naidoo M., Ramdharee P., Selibea Y., Sewpersad S., Sham S., Wessels J. D., Africander C., Bejia T., Blakemore S. P., Botes M., Bunwarie B., Hernandez C. B., Jeeraz M. A., Legutko D. A., Lopez A. G., De Meyer J. N., Muzenda T., Naidoo N., Patel M., Pentela R., Junge M., Mansoor N., Rademan L., Scislowski P., Seedat I., Van Den Berg B., Van Der Merwe D., Van Wyk S., Govender K., Naicker D., Ramjee R., Saley M., Kuhn W. P., Matos-Puig R., Moolla Z., Lisi A., Perez G., Beltran A. V., Lozano A., Navarro C. D., Duca A., Ernesto E. P. M., Ferrando C., Fuentes I., Garcia-Perez M. L., Gracia E., Palomares A. I., Katime A., Minana A., Incertis R. R., Romero E., Garcia C. S. R., Rubio C., Artiles T. S., Soro M., Valls P., Laguarda G. A., Benavent P., Cuenca V. C., Cueva A., Lafuente M., Parra A. M., Rodrigo A. R., Sanchez-Morcillo S., Tormo S., Redondo F. J., De Andres Ibanez J. A., Diago L. G., Cadiz M. J. 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K., Karpate, S., O'Hara, C., Troko, J., Angus, K., Bradley, J., Brennan, E., Brooks, C., Brown, J., Brown, G., Finch, A., Gratrix, K., Hesketh, S., Hill, G., Jeffs, C., Morgan, M., Pemberton, C., Slawson, N., Spickett, H., Swarbrick, G., Van Duyvenvoorde, G., Brennan, A., Briscoe, R., Cooper, S., Lawton, T., Northey, M., Senaratne, R., Stanworth, H., Burrows, L., Cain, H., Craven, R., Davies, K., Jonas, A., Pachucki, M., Walkden, G., Davies, H., Gudaca, M., Hobrok, M., Arawwawala, D., Fergey, L., Gardiner, M., Gunn, J., Johnson, L., Lofting, A., Lyle, A., Neela, F. M., Smolen, S., Topliffe, J., Williams, S., Bland, M., Balaji, P., Kaura, V., Lanka, P., Naylor, C., Ahmed, A., Myatt, J., Shenoy, R., Soon, W. C., Tan, J., Karadia, S., Self, J., Durant, E., Tripathi, S., Bullock, C., Ghosh, A., Hughes, T., Zsisku, L., Bengeri, S., Cowton, A., Khalid, M. S., Limb, J., Mcadam, C., Porritt, M., Rafi, M. A., Shekar, P., Adams, D., Harden, C., Hollands, H., King, A., March, L., Minto, G., Patrick, A., Squire, R., Waugh, D., Kumara, P., Simeson, K., Yarwood, J., Browning, J., Hatton, J., Julian, H., Mitra, A., Newton, M., Pernu, P. K., Wilson, A., Commey, T., Foot, H., Glover, L., Gupta, A., Lancaster, N., Levin, J., Mackenzie, F., Mestanza, C., Nofal, E., Pout, L., Varden, R., Wild, J., Jones, S., Moreton, S., Pulletz, M., Davies, C., Martin, M., Thomas, S., Burns, K., Mcarthur, C., Patel, P., Lau, G., Rich, N., Davis, F., Lyons, R., Port, B., Prout, R., Smith, C., Adelaja, Y., Bennett, V., Bidd, H., Dumitrescu, A., Fox, J., Keen, A., Mguni, N., Ong, C., Adams, G., Boshier, P., Brown, R., Butryn, I., Chatterjee, J., Freethy, A., Lockwood, G., Tsakok, M., Tsiligiannis, S., Peat, W., Stephenson, L., Bradburn, M., Pick, S., Cunha, P., Olagbaiye, O., Tayeh, S., Packianathaswamy, B., Abernethy, C., Balasubramaniam, M., Bennett, R., Bolton, D., Martinson, V., Bell, S., Heather, B., Kushakovsky, V., Alcock, L., Alexander, H., Anderson, C., Baker, P., Brookes, M., Cawthorn, L., Cirstea, E., Clarkson, R., Colling, K., Coulter, I., Das, S., Haigh, K., Hamdan, A., Hugill, K., Kottam, L., Lisseter, E., Mawdsley, M., Mcgivern, J., Padala, K., Phelps, V., Kumar, V. R., Stewart, K., Towse, K., Tregonning, J., Vahedi, A., Walker, A., Baines, D., Bilolikar, A., Chande, S., Copley, E., Dunk, N., Kulkarni, R., Kumar, P., Metodiev, Y., Ncomanzi, D., Raithatha, B., Raymode, P., Szafranski, J., Twohey, L., Watt, P., Weatherall, L., Weatherill, J., Whitman, Z., Wighton, E., Abayasinghe, C., Chan, A., Darwish, S., Gill, J., Glasgow, E., Hadfield, D., Harris, C., Hopkins, P., Kochhar, A., Kunst, G., Mellis, C., Pool, A., Riozzi, P., Selman, A., Smith, E. -J., Vele, L., Gercek, Y., Guy, K., Holden, D., Watson, N., Whysall, K., Andreou, P., Hales, D., Thompson, J., Bowrey, S., Mcdonald, S., Gilmore, J., Hills, V., Kelly, C., Kelly, S., Lloyd, G., Abbott, T., Gall, L., Torrance, H., Vivian, M., Berntsen, E., Nolan, T., Turner, A., Vohra, A., Brown, A., Clark, R., Coughlan, E., Daniel, C., Patvardhan, C., Pearson, R., Predeep, S., Saad, H., Shanmugam, M., Varley, S., Wylie, K., Cooper, L., Makowski, A., Misztal, B., Moldovan, E., Pegg, C., Donovan, A., Foot, J., Large, S., Claxton, A., Netke, B., Armstrong, R., Calderwood, C., Kwok, A., Mohr, O., Oyeniyi, P., Patnaik, L., Post, B., Ali, S., Arshad, H., Baker, G., Brenner, L., Brincat, M., Brunswicker, A., Cox, H., Cozar, O. I., Cheong, E., Durst, A., Fengas, L., Flatt, J., Glister, G., Narwani, V., Photi, E., Rankin, A., Rosbergen, M., Beaton, C., Horn, R., Hunt, J., Rousseau, G., Stancombe, L., Absar, M., Allsop, J., Drinkwater, Z., Hodgkiss, T., Smith, K., Alexander-Sefre, F., Campey, L., Dudgeon, L., Hall, K., Hitchcock, R., James, L., Winstone, U., Ahmad, N., Bauchmuller, K., Harrison, J., Jeffery, H., Miller, D., Pinder, A., Pothuneedi, S., Rosser, J., Sanghera, S., Swift, D., Walker, R., Bester, D., Cavanagh, S., Cripps, H., Daniel, H., Lynch, J., Pyke, S., Scholefield, J., Whitworth, H., Bottrill, F., Ramalingam, G., Webb, S., Akerman, N., Antill, P., Bourner, L., Buckley, S., Castle, G., Charles, R., Eggleston, C., Foster, R., Gill, S., Lindley, K., Lklouk, M., Lowery, T., Martin, O., Milne, D., O'Connor, P., Ratcliffe, A., Rose, A., Smith, A., Varma, S., Ward, J., Barcraft-Barnes, H., Camsooksai, J., Colvin, C., Reschreiter, H., Tbaily, L., Venner, N., Hamilton, C., Kelly, L., Toth-Tarsoly, P., Dodsworth, K., Foord, D., Gordon, P., Hawes, E., Lamb, N., Mouland, J., Nightingale, J., Rose, S., Schrieber, J., Al 'Amri, K., Aladin, H., Arshad, M. A., Barraclough, J., Bentley, C., Bergin, C., Carrera, R., Clarkson, A., Collins, M., Denham, S., Griffiths, E., Ip, P., Jeyanthan, S., Joory, K., Kaur, S., Marriott, P., Mitchell, N., Nagaiah, S., Nilsson, A., Parekh, N., Pope, M., Seager, J., Serag, H., Tameem, A., Thomas, A., Thunder, J., Torrance, A., Vohra, R., Whitehouse, A., Wong, T., Blunt, M., Wong, K., Giles, J., Reed, I., Weller, D., Bell, G., Birch, J., Damant, R., Maiden, J., Mewies, C., Prince, C., Radford, J., Reynolds, T., Balain, B., Banerjee, R., Barnett, A., Burston, B., Edwards, J., Evans, C., Ford, D., Gallacher, P., Hill, S., Jaffray, D., Karlakki, S., Kennedy, J., Kiely, N., Lewthwaite, S., Marquis, C., Ockendon, M., Phillips, S., Pickard, S., Richardson, J., Roach, R., Smith, T., Spencer-Jones, R., Steele, N., Steen, J., Van Liefland, M., White, S., Faulds, M., Harris, M., Nicol, S., Pearson, S. A., Chukkambotla, S., Andrew, A., Attrill, E., Campbell, G., Datson, A., Fouracres, A., Graterol, J., Graves, L., Hong, B., Ishimaru, A., Karthikeyan, A., King, H., Lawson, T., Lee, G., Lyons, S., Hall, A. M., Mathoulin, S., Mcintyre, E., Mclaughlin, D., Mulcahy, K., Paddle, J., Robbins, J., Sung, W., Tayo, A., Trembath, L., Venugopal, S., Wigmore, G., Boereboom, C., Downes, C., Humphries, R., Melbourne, S., Tou, S., Ullah, S., Batchelor, N., Boxall, L., Broomby, R., Deen, T., Hellewell, A., Helliwell, L., Hutchings, M., Hutchins, D., Keenan, S., Mackie, D., Potter, A., Smith, F., Stone, L., Thorpe, K., Wassall, R., Woodgate, A., Baillie, S., Campbell, T., James, S., King, C., De Araujo, D. M., Martin, D., Morkane, C., Neely, J., Rajendram, R., Burton, M., James, K., Keevil, E., Minik, O., Morgan, J., Musgrave, A., Rajanna, H., Roberts, T., Adamson, M., Jumbe, S., Kendall, J., Muthuswamy, M. B., Cruikshanks, A., Wrench, I., Zeidan, L., Ardern, D., Harris, B., Hellstrom, J., Martin, J., Thomas, R., Varsani, N., Brown, C. W., Docherty, P., Gillies, M., Mcgregor, E., Usher, H., Craig, J., Bodger, P., Creary, T., Everingham, K., Fowler, A., Hewson, R., Ijuo, E., Januszewska, M., Jones, T., Kantsedikas, I., Lahiri, S., Mclean, A. L., Niebrzegowska, E., Phull, M., Wickboldt, N., Baldwin, J., Doyle, D., Mcmullan, S., Oladapo, M., Owen, T., Williams, A., Gregory, P., Husain, T., Kirk-Bayley, J., Mathers, E., Montague, L., Harper, M., Jack, J., Ridley, C., Avis, J., Cook, T., Dali-Kemmery, L., Kerslake, I., Lambourne, V., Pearson, A., Boyd, C., Callaghan, M., Lawson, C., Mccrossan, R., Nesbitt, V., O'Connor, L., Sinclair, R., Farid, N., Morgese, C., Bhatia, K., Karmarkar, S., Ahmed, J., Branagan, G., Hutton, M., Swain, A., Brookes, J., Cornell, J., Dolan, R., Hulme, J., Van Vuuren, A. J., Jowitt, T., Kalashetty, G., Lloyd, F., Kiran, Patel, Sherwood, N., Brown, L., Chandler, B., Deighton, K., Emma, T., Haunch, K., Cheeseman, M., Dent, K., Gray, C., Hood, M., Jones, D., Juj, J., Rao, R., Walker, T., Al Anizi, M., Cheah, C., Cheing, Y., Coutinho, F., Gondo, P., Hadebe, B., Hove, M. O., Khader, A., Krishnachetty, B., Rhodes, K., Sokhi, J., Baker, K. -A., Bertram, W., Looseley, A., Mouton, R., Hanna, G., Arnold, G., Arya, S., Balfoussia, D., Baxter, L., Harris, J., Jones, C., Knaggs, A., Markar, S., Perera, A., Scott, A., Shida, A., Sirha, R., Wright, S., Frost, V., Andrews, E., Arrandale, L., Barrett, S., Cifra, E., Cooper, M., Dragnea, D., Elna, C., Maclean, J., Meier, S., Milliken, D., Munns, C., Ratanshi, N., Ramessur, S., Salvana, A., Watson, A., Ali, H., Critchley, R., Endersby, S., Hicks, C., Liddle, A., Pass, M., Ritchie, C., Thomas, C., Too, L., Welsh, S., Gill, T., Johnson, J., Reed, J., Davis, E., Papadopoullos, S., Attwood, C., Biffen, A., Boulton, K., Gray, S., Hay, D., Mills, S., Montgomery, J., Riddell, R., Simpson, J., Bhardwaj, N., Paul, E., Uwubamwen, N., Alexander, M., Arrich, J., Arumugam, S., Blackwood, D., Boggiano, V., Lam, Y., Chatterjee, D., Chhabra, A., Christian, R., Costelloe, H., Matthewman, M. C., Dalton, E., Darko, J., Davari, M., Dave, T., Deacon, M., Deepak, S., Edmond, H., Ellis, J., El-Sayed, A., Eneje, P., English, R., Ewe, R., Foers, W., Franklin, J., Gallego, L., Garrett, E., Goldberg, O., Goss, H., Greaves, R., Harris, R., Hennings, C., Jones, E., Kamali, N., Kokkinos, N., Lewis, C., Lignos, L., Malgapo, E. V., Malik, R., Milne, A., Mulligan, J. -P., Nicklin, P., Palipane, N., Parsons, T., Piper, R., Prakash, R., Ramesh, B., Rasip, S., Reading, J., Rela, M., Reyes, A., Stephens, R., Rooms, M., Shah, K., Simons, H., Solanki, S., Spowart, E., Stevens, A., Waggett, H., Yassaee, A., Kennedy, A., Scott, S., Somanath, S., Berg, A., Hernandez, M., Nanda, R., Tank, G., Wilson, N., Wilson, D., Al-Soudaine, Y., Baldwin, M., Cornish, J., Davies, Z., Davies, L., Edwards, M., Frewer, N., Gallard, S., Glasbey, J., Harries, R., Hopkins, L., Kim, T., Koompirochana, V., Lawson, S., Lewis, M., Makzal, Z., Scourfield, S., Ahmad, Y., Bates, S., Blackwell, C., Bryant, H., Collins, H., Coulter, S., Cruickshank, R., Daniel, S., Daubeny, T., Golder, K., Hawkins, L., Helen, B., Hinxman, H., Levett, D., Salmon, K., Seaward, L., Ben, L., Tyrell, B., Wadams, B., Walsgrove, J., Dickson, J., Constantin, K., Karen, M., O'Brien, P., O'Donohoe, L., Payne, H., Sundayi, S., Walker, E., Brooke, J., Cardy, J., Humphreys, S., Kessack, L., Kubitzek, C., Kumar, S., Cotterill, D., Hodzovic, E., Hosdurga, G., Miles, E., Saunders, G., Campbell, M., Chan, P., Jemmett, K., Raj, A., Naik, A., Oshowo, A., Ramamoorthy, R., Shah, N., Sylvan, A., Blyth, K., Burtenshaw, A., Freeman, D., Johnson, E., Lo, P., Martin, T., Plunkett, E., Wollaston, J., Allison, J., Carroll, C., Craw, N., Craw, S., Pitt-Kerby, T., Rowland-Axe, R., Spurdle, K., Mcdonald, A., Simon, D., Sinha, V., Banner-Goodspeed, V., Boone, M., Campbell, K., Lu, F., Scannell, J., Sobol, J., Balajonda, N., Clemmons, K., Conde, C., Elgasim, M., Funk, B., Hopkins, T., Olaleye, O., Omer, O., Pender, M., Porto, A., Waweru, P., Yeh, E., Bodansky, D., Evans, A., Kleopoulos, S., Maril, R., Mathney, E., Sanchez, A., Tinuoye, E., Bateman, B., Eng, K., Jiang, N., Ladha, K., Needleman, J., Chen, L. -L., Lane, R., Robinowitz, D., Ghushe, N., Irshad, M., O'Connor, J., Patel, S., Takemoto, S., Wallace, A., Mazzeffi, M., Rock, P., Wallace, K., Chua, P., Mattera, M., Sharar, R., Thilen, S., Treggiari, M., Morgan, A., Sofjan, I., Subramaniam, K., Avidan, M., Maybrier, H., Muench, M., and Wildes, T.
Subjects: operative, Male, Pediatrics, GLOBAL HEALTH, Cohort Studies, 0302 clinical medicine, Postoperative Complications, 030202 anesthesiology, surgical procedures, operative, mortality, Health care, statistics and numerical data, 030212 general & internal medicine, Hospital Mortality, Prospective Studies, Prospective cohort study, Aged, 80 and over, HIGH-RISK SURGERY, COMPLICATIONS, OUTCOMES, Incidence (epidemiology), Middle Aged, PATIENT MORTALITY, Female, SURGICAL MORTALITY, Cohort study, Adult, medicine.medical_specialty, methods, 03 medical and health sciences, Anesthesiology, medicine, QUALITY, Humans, Elective surgery, postoperative care, statistics and numerical data, Aged, Quality of Health Care, Postoperative Care, business.industry, Postoperative complication, mortality, CANCER-SURGERY, surgical procedures, Anesthesiology and Pain Medicine, Logistic Models, VOLUME, postoperative care, methods, Human medicine, Complication, business
Abstract: Background.The incidence and impact of postoperative complications are poorly described. Failure-to-rescue, the rate of death following complications, is an important quality measure for perioperative care but has not been investigated across multiple health care systems.Methods.We analysed data collected during the International Surgical Outcomes Study, an international 7-day cohort study of adults undergoing elective inpatient surgery. Hospitals were ranked by quintiles according to surgical procedural volume (Q1 lowest to Q5 highest). For each quintile we assessed in-hospital complications rates, mortality, and failure-to-rescue. We repeated this analysis ranking hospitals by risk-adjusted complication rates (Q1 lowest to Q5 highest).Results.A total of 44 814 patients from 474 hospitals in 27 low-, middle-, and high-income countries were available for analysis. Of these, 7508 (17%) developed one or more postoperative complication, with 207 deaths in hospital (0.5%), giving an overall failure-to-rescue rate of 2.8%. When hospitals were ranked in quintiles by procedural volume, we identified a three-fold variation in mortality (Q1: 0.6% vs Q5: 0.2%) and a two-fold variation in failure-to-rescue (Q1: 3.6% vs Q5: 1.7%). Ranking hospitals in quintiles by risk-adjusted complication rate further confirmed the presence of important variations in failure-to-rescue, indicating differences between hospitals in the risk of death among patients after they develop complications.Conclusions.Comparison of failure-to-rescue rates across health care systems suggests the presence of preventable postoperative deaths. Using such metrics, developing nations could benefit from a data-driven approach to quality improvement, which has proved effective in high-income countries.
Published: 2017
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36. Mapping individual differences across brain network structure to function and behavior with connectome embedding

Author: Joshua Faskowitz, Olaf Sporns, Galia Avidan, and Gidon Levakov
Subjects: Adult, Male, Theoretical computer science, Adolescent, Computer science, Cognitive Neuroscience, Intelligence, Longevity, Individuality, Neurosciences. Biological psychiatry. Neuropsychiatry, Context (language use), Article, Functional connectivity, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Connectome, Image Processing, Computer-Assisted, Humans, Child, Representation (mathematics), Aged, 030304 developmental biology, Aged, 80 and over, Structure (mathematical logic), Behavior, Brain Mapping, 0303 health sciences, Structural connectivity, Function (mathematics), Middle Aged, Magnetic Resonance Imaging, Generative model, Diffusion Tensor Imaging, Neurology, Individual differences, Embedding, Graph (abstract data type), Female, Nerve Net, 030217 neurology & neurosurgery, RC321-571
Abstract: The connectome, a comprehensive map of the brain’s anatomical connections, is often summarized as a matrix comprising all dyadic connections among pairs of brain regions. This representation cannot capture higher-order relations within the brain graph. Connectome embedding (CE) addresses this limitation by creating compact vectorized representations of brain nodes capturing their context in the global network topology. Here, nodes “context” is defined as random walks on the brain graph and as such, represents a generative model of diffusive communication around nodes. Applied to group-averaged structural connectivity, CE was previously shown to capture relations between inter-hemispheric homologous brain regions and uncover putative missing edges from the network reconstruction. Here we extend this framework to explore individual differences with a novel embedding alignment approach. We test this approach in two lifespan datasets (NKI: n=542; Cam-CAN: n=601) that include diffusion-weighted imaging, resting-state fMRI, demographics and behavioral measures. We demonstrate that modeling functional connectivity with CE substantially improves structural to functional connectivity mapping both at the group and subject level. Furthermore, age-related differences in this structure-function mapping are preserved and enhanced. Importantly, CE captures individual differences by out-of-sample prediction of age and intelligence. The resulting predictive accuracy was higher compared to using structural connectivity and functional connectivity. We attribute these findings to the capacity of the CE to incorporate aspects of both anatomy (the structural graph) and function (diffusive communication). Our novel approach allows mapping individual differences in the connectome through structure to function and behavior.
Published: 2021
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37. Interest in technology among medical students early in their clinical experience

Author: Alexander Avidan, Rachel Yaffa Zisk-Rony, and Charles Weissman
Subjects: Male, Technology, Students, Medical, 020205 medical informatics, media_common.quotation_subject, education, Specialty, Face (sociological concept), Health Informatics, 02 engineering and technology, 03 medical and health sciences, 0302 clinical medicine, Artificial Intelligence, Surveys and Questionnaires, ComputingMilieux_COMPUTERSANDEDUCATION, 0202 electrical engineering, electronic engineering, information engineering, Information system, Humans, Social media, 030212 general & internal medicine, media_common, Response rate (survey), Medical education, Career Choice, Medical practice, Internship and Residency, Future career, Creativity, Female
Abstract: Background The world is in the midst of the “digital” revolution characterized by the ascendency of computerization, information systems and artificial intelligence with an emphasis on innovation and creativity. This revolution has affected current medical practice and promises to significantly impact it in the future. This requires physician’s understanding and participation in adopting such technology. This study aimed to explore the role technology plays in the future career plans of medical students. Methods A questionnaire examining selection criteria for medical specialty choice, criteria for choosing a post-residency job and demographic data was completed by a convenience sample of 5th-year Israeli medical students. Results Two-hundred forty-two students (51 % men) completed the questionnaire, an 84 % response rate. Only a third (35 %) rated the specialty selection criterion "provides mechanical/ technological challenges" as important, while only 7% considered as important that a specialty requires skills in computer science. Few students were interested in post-residency positions requiring much technological knowledge (25 %) and requiring much skill with computerized information systems (13 %). Male students were significantly more interested than females in such positions and these students more often reported that they were considering careers in surgery and its subspecialties. This surgical bent was confirmed by the 42 % of students interested in post-residency positions that include time in the operating room having more interest in positions requiring much technological knowledge than the students not interested in operating room time. Conclusions This preliminary study demonstrated that as a group the students’ expressed relatively little interest in medical specialties and post-residency positions involving technological challenges and knowledge of information (computer) science. Yet, the sub-group interested in the surgical specialties had such interests. These findings were perplexing since the students belong to Generations Y and Z who are steeped in the use of smartphones and social media. Therefore, we failed to support our hypothesis that Generation Y and Z students would be attracted to specialties and positions that provide them with technological challenges. Furthermore, medical educators need to explore this apparent lack of interest in technology in order to insure that the future physician workforce is ready to face future “digital” challenges.
Published: 2020

38. The COVID-19 pandemic masks the way people perceive faces

Author: R. Shayna Rosenbaum, Erez Freud, Andreja Stajduhar, Tzvi Ganel, and Galia Avidan
Subjects: Adult, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Adolescent, Science, Social Interaction, Facial recognition system, Article, 050105 experimental psychology, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Face perception, Pregnancy, Activities of Daily Living, Human behaviour, Humans, 0501 psychology and cognitive sciences, Memory test, 10. No inequality, Pandemics, Aged, Multidisciplinary, SARS-CoV-2, 05 social sciences, Masks, COVID-19, Recognition, Psychology, Middle Aged, Social relation, Face masks, Face (geometry), Medicine, Female, Perception, Psychology, Facial Recognition, 030217 neurology & neurosurgery, Cognitive psychology
Abstract: The unprecedented effort to minimize the effects of the COVID-19 pandemic introduces a new arena for human face recognition in which faces are partially occluded with masks. Here, we tested the extent to which face masks change the way faces are perceived. To this end, we evaluated face processing abilities for masked and unmasked faces in a large online sample of adult observers (n=496) using an adapted version of the Cambridge Face Memory Test, the mostvalidated measure of face perception abilities in humans. As expected, a substantial decrease in performance was found for masked faces, along with a large increase in the proportion of individuals who exhibit a remarkable deficit in face perception. Unexpectedly, however, the inclusion of masks led to a qualitative change in the way masked faces are perceived. In particular, holistic processing, the hallmark of face perception, was severely impaired for maskedfaces. Similar changes were found when masks were included either during the study or the test phases of the experiment. Together, we provide robust evidence for qualitative alterations in the processing of masked faces that could have significant effects on daily activities and social interactions.
Published: 2020
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39. Fasciculation frequency at the biceps brachii and brachialis muscles is associated with amyotrophic lateral sclerosis disease burden and activity

Author: Vivian E. Drory, Vera Bril, Reuven Avidan, Alon Abraham, and Yaara Fainmesser
Subjects: 0301 basic medicine, Male, medicine.medical_specialty, Time Factors, Physiology, 030105 genetics & heredity, Fasciculation, Biceps, Severity of Illness Index, Neuromuscular ultrasound, Quadriceps Muscle, Manual Muscle Testing, 03 medical and health sciences, Cellular and Molecular Neuroscience, 0302 clinical medicine, Physiology (medical), Internal medicine, medicine, Humans, Muscle Strength, Amyotrophic lateral sclerosis, Muscle, Skeletal, Disease burden, Aged, Ultrasonography, Biceps brachii muscle, business.industry, Amyotrophic Lateral Sclerosis, Organ Size, Middle Aged, medicine.disease, Hand, Cardiology, Arm, Disease Progression, Brachialis, Female, Neurology (clinical), medicine.symptom, business, 030217 neurology & neurosurgery
Abstract: Introduction Fasciculations are most commonly seen in the biceps brachii muscle in amyotrophic lateral sclerosis (ALS). In this study we explored the association between fasciculation frequency in a single location - biceps brachii and brachialis muscles (BB), and disease burden and activity METHODS: Sonographic muscle studies were performed in 90 ALS patients, 47 of whom were seen in subsequent follow-up. The association between fasciculations frequency at the BB and ALS Functional Rating Scale Revised (ALSFRS-R) and Manual Muscle Testing (MMT) scores was determined. Results High fasciculation frequency at the BB, where detection rate was the highest, was associated with shorter disease duration, greater muscle thickness, higher MMT scores, and faster rate of decline in ALSFRS-R initially, and MMT subsequently. Discussion High fasciculation frequency at the BB as determined by sonography, is associated with less impairment at time of examination, and a more active disease with a more rapid progression.
Published: 2020

40. Preoperative cognitive abnormality, intraoperative electroencephalogram suppression, and postoperative delirium: A mediation analysis

Author: Fritz, Bradley A, King, Christopher R, Abdallah, Arbi Ben, Lin, Nan, Mickle, Angela M, Budelier, Thaddeus P, Oberhaus, Jordan, Park, Daniel, Maybrier, Hannah R, Wildes, Troy S, and Avidan, Michael S
Subjects: Male, Emergence Delirium, Monitoring, Intraoperative, mental disorders, Preoperative Period, Humans, Cognitive Dysfunction, Electroencephalography, Female, Article, Aged
Abstract: Postoperative delirium is a common complication that hinders recovery after surgery. Intraoperative electroencephalogram suppression has been linked to postoperative delirium, but it is unknown if this relationship is causal or if electroencephalogram suppression is merely a marker of underlying cognitive abnormalities. The hypothesis of this study was that intraoperative electroencephalogram suppression mediates a nonzero portion of the effect between preoperative abnormal cognition and postoperative delirium.This is a prespecified secondary analysis of the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized trial, which enrolled patients age 60 yr or older undergoing surgery with general anesthesia at a single academic medical center between January 2015 and May 2018. Patients were randomized to electroencephalogram-guided anesthesia or usual care. Preoperative abnormal cognition was defined as a composite of previous delirium, Short Blessed Test cognitive score greater than 4 points, or Eight Item Interview to Differentiate Aging and Dementia score greater than 1 point. Duration of intraoperative electroencephalogram suppression was defined as number of minutes with suppression ratio greater than 1%. Postoperative delirium was detected via Confusion Assessment Method or chart review on postoperative days 1 to 5.Among 1,113 patients, 430 patients showed evidence of preoperative abnormal cognition. These patients had an increased incidence of postoperative delirium (151 of 430 [35%] vs.123 of 683 [18%], P0.001). Of this 17.2% total effect size (99.5% CI, 9.3 to 25.1%), an absolute 2.4% (99.5% CI, 0.6 to 4.8%) was an indirect effect mediated by electroencephalogram suppression, while an absolute 14.8% (99.5% CI, 7.2 to 22.5%) was a direct effect of preoperative abnormal cognition. Randomization to electroencephalogram-guided anesthesia did not change the mediated effect size (P = 0.078 for moderation).A small portion of the total effect of preoperative abnormal cognition on postoperative delirium was mediated by electroencephalogram suppression. Study precision was too low to determine if the intervention changed the mediated effect.
Published: 2020

41. Association Between Preoperative Obstructive Sleep Apnea and Preoperative Positive Airway Pressure With Postoperative Intensive Care Unit Delirium

Author: Bradley A. Fritz, Michael S. Avidan, Yo-El Ju, Christopher R. King, Krisztina E Escallier, Ben J.A. Palanca, Sherry L. McKinnon, and Nan Lin
Subjects: Adult, Male, medicine.medical_specialty, Population, urologic and male genital diseases, Preoperative care, behavioral disciplines and activities, law.invention, Positive-Pressure Respiration, Postoperative Complications, law, Anesthesiology, Risk Factors, Positive airway pressure, mental disorders, medicine, Humans, education, Original Investigation, Aged, Retrospective Studies, education.field_of_study, Sleep Apnea, Obstructive, business.industry, Research, Sleep apnea, Apnea, Delirium, General Medicine, Middle Aged, medicine.disease, Intensive care unit, respiratory tract diseases, nervous system diseases, Obstructive sleep apnea, Online Only, Emergency medicine, Preoperative Period, Female, medicine.symptom, business
Abstract: Key Points Question Is there an association between obstructive sleep apnea and delirium after major surgery? Findings In this cohort study of 7792 patients admitted to the intensive care unit after surgery, 26% had obstructive sleep apnea, and delirium occurred in 47%. After risk adjustment, there was no significant association between obstructive sleep apnea and postoperative delirium. Meaning This study found no association between obstructive sleep apnea and delirium in patients admitted postoperatively to the intensive care unit., Importance Obstructive sleep apnea has been associated with postoperative delirium, which predisposes patients to major adverse outcomes. Positive airway pressure may be an effective intervention to reduce delirium in this population. Objectives To determine if preoperative obstructive sleep apnea is associated with postoperative incident delirium in the intensive care unit and if preoperative positive airway pressure adherence modifies the association. Design, Setting, and Participants A retrospective single-center cohort study was conducted at a US tertiary hospital from November 1, 2012, to August 31, 2016, among 7792 patients admitted to an intensive care unit who underwent routine Confusion Assessment Method for the intensive care unit after major surgery. Patients were adults who had undergone a complete preoperative anesthesia assessment, received general anesthesia, underwent at least 1 delirium assessment, were not delirious preoperatively, and had a preoperative intensive care unit stay of less than 6 days. Statistical analysis was conducted from August 20, 2019, to January 11, 2020. Exposures Self-reported obstructive sleep apnea, billing diagnosis of obstructive sleep apnea, or STOP-BANG (Snoring, Tiredness, Observed Apnea, Blood Pressure, Body Mass Index, Age, Neck Circumference and Gender) questionnaire score greater than 4, as well as self-reported use of preoperative positive airway pressure. Main Outcomes and Measures Delirium within 7 days of surgery. Results A total of 7792 patients (4562 men; mean [SD] age, 59.2 [15.3] years) met inclusion criteria. Diagnosed or likely obstructive sleep apnea occurred in 2044 patients (26%), and delirium occurred in 3637 patients (47%). The proportion of patients with incident delirium was lower among those with obstructive sleep apnea than those without (897 of 2044 [44%] vs 2740 of 5748 [48%]; unadjusted risk difference, −0.04; 99% credible interval [CrI], −0.07 to −0.00). Positive airway pressure adherence had minimal association with delirium (risk difference, −0.00; 99% CrI, −0.09 to 0.09). Doubly robust confounder adjustment eliminated the association between obstructive sleep apnea and delirium (risk difference, −0.01; 99% CrI, −0.04 to 0.03) and did not change that of preoperative positive airway pressure adherence (risk difference, −0.00, 99% CrI, −0.07 to 0.07). The results were consistent across multiple sensitivity analyses. Conclusions and Relevance After risk adjustment, this study found no association between obstructive sleep apnea and postoperative delirium in the context of usual care in the intensive care unit, with 99% CrIs excluding clinically meaningful associations. With limited precision, no association was found between positive airway pressure adherence and delirium. Selection bias and measurement error limit the validity and generalizability of these observational associations; however, they suggest that interventions targeting sleep apnea and positive airway pressure are unlikely to have a meaningful association with postoperative intensive care unit delirium., This cohort study examines whether preoperative obstructive sleep apnea is associated with postoperative incident delirium in the intensive care unit (ICU) and if preoperative positive airway pressure adherence modifies the association.
Published: 2020

42. Brain network motifs are markers of loss and recovery of consciousness

Author: Catherine Duclos, Giancarlo Vanini, Danielle Nadin, Goodarz Golmirzaie, Max B. Kelz, Paul Picton, Ellen Janke, Yacine Mahdid, George A. Mashour, Vijay Tarnal, Stefanie Blain-Moraes, and Michael S. Avidan
Subjects: 0301 basic medicine, Adult, Male, Consciousness, Brain activity and meditation, media_common.quotation_subject, Science, Electroencephalography, Biology, Article, 03 medical and health sciences, Functional brain, Young Adult, 0302 clinical medicine, Motif (narrative), 030202 anesthesiology, medicine, Humans, Clustering coefficient, media_common, Brain network, Neural correlates of consciousness, Multidisciplinary, medicine.diagnostic_test, Unconsciousness, Brain, Diagnostic markers, Translational research, Phase lag, Healthy Volunteers, 030104 developmental biology, Anesthetic, Anesthesia Recovery Period, Medicine, Female, medicine.symptom, Nerve Net, Psychology, Neuroscience, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background: Motifs are patterns of inter-connections between nodes of a complex network, and have been investigated as the basic building blocks of directed networks. This study explored the re-organization of 3-node (i.e. 3-electrode) network motifs during anesthetic-induced loss and recovery of consciousness. We hypothesized that motif frequency and topography would change across states of consciousness, and that the frequency and topography associated with consciousness would recover prior to the return of behavioral responsiveness. Methods: Nine healthy subjects underwent a 3-hour controlled anesthetic protocol (propofol induction; isoflurane maintenance) in an operating room, while brain activity was recorded through 128-channel electroencephalography (EEG). In the alpha (8-13 Hz) frequency band, five-minute epochs of EEG were extracted for: baseline; induction; unconsciousness; 30-, 10- and 5-minutes pre-recovery of consciousness; 30- and 180-minutes post-recovery of consciousness. We constructed a functional brain network using the weighted phase lag index and the directed phase lag index, which were then used to calculate graph theoretical brain network properties and the frequency and topography of 3-node (i.e. 3-electrode) motifs. Results: Three motifs (motifs 1, 2 and 5) were significantly present across participants and epochs, when compared to random networks (p
Published: 2020

43. Methylome and transcriptome profiling in Myasthenia Gravis monozygotic twins

Author: Marc H. De Baets, Sonia Berrih-Aknin, Laurent Servais, Frédérique Truffault, Nili Avidan, Bruno Eymard, Ariel Miller, Shimrat Mamrut, Mélinée Frenkian, Jiri Pitha, Elsebeth Staun-Ram, Tarek Sharshar, MUMC+: MA Med Staf Spec CTC (9), and RS: MHeNs - R3 - Neuroscience
Subjects: 0301 basic medicine, TREM-1, Bisulfite sequencing, Predisposition, Autoimmunity, Monocytes, Epigenesis, Genetic, Transcriptome, 0302 clinical medicine, IDENTICAL-TWINS, Immunology and Allergy, WIDE ASSOCIATION, Disease chronicity, DNA METHYLATION, DIFFERENTIALLY METHYLATED REGIONS, Genetics, THYMUS, Methylation, Middle Aged, Resolution of inflammation, EPIGENETICS, DNA methylation, Female, Signal Transduction, Adult, EXPRESSION, Immunology, Biology, 03 medical and health sciences, Young Adult, Myasthenia Gravis, Genetic predisposition, Humans, Genetic Predisposition to Disease, Epigenetics, Gene, Genetic Association Studies, Aged, Gene Expression Profiling, Twins, Monozygotic, Triggering Receptor Expressed on Myeloid Cells-1, RHEUMATOID-ARTHRITIS, 030104 developmental biology, Differentially methylated regions, Case-Control Studies, Monocyte function, T-CELLS, CpG Islands, 030217 neurology & neurosurgery, Biomarkers
Abstract: Objective: To identify novel genetic and epigenetic factors associated with Myasthenia gravis (MG) using an identical twins experimental study design.Methods: The transcriptome and methylome of peripheral monocytes were compared between mono zygotic (MZ) twins discordant and concordant for MG, as well as with MG singletons and healthy controls, all females. Sets of differentially expressed genes and differentially methylated CpGs were validated using RT-PCR for expression and target bisulfite sequencing for methylation on additional samples.Results: >100 differentially expressed genes and similar to 1800 differentially methylated CpGs were detected in peripheral monocytes between MG patients and controls. Several transcripts associated with immune homeostasis and inflammation resolution were reduced in MG patients. Only a relatively few genes differed between the discordant healthy and MG co-twins, and both their expression and methylation profiles demonstrated very high similarity.Interpretation: This is the first study to characterize the DNA methylation profile in MG, and the expression profile of immune cells in MZ twins with MG. Results suggest that numerous small changes in gene expression or methylation might together contribute to disease. Impaired monocyte function in MG and decreased expression of genes associated with inflammation resolution could contribute to the chronicity of the disease. Findings may serve as potential new predictive biomarkers for disease and disease activity, as well as potential future targets for therapy development. The high similarity between the healthy and the MG discordant twins, suggests that a molecular signature might precede a clinical phenotype, and that genetic predisposition may have a stronger contribution to. disease than previously assumed. (C) 2017 Elsevier Ltd. All rights reserved.
Published: 2020

44. The Parental Experience of Newborns With Neonatal Abstinence Syndrome Across Inpatient Care Settings: A Qualitative Study

Author: Amy Buczkowski, David F. Cox, Olivia Avidan, and Alexa Craig
Subjects: Parents, medicine.medical_specialty, Neonatal intensive care unit, 01 natural sciences, 03 medical and health sciences, 0302 clinical medicine, Neonatal abstinence, New England, Pregnancy, Medicine, Humans, Pharmacology (medical), 030212 general & internal medicine, 0101 mathematics, Inpatients, Inpatient care, business.industry, 010102 general mathematics, Infant, Newborn, medicine.disease, Substance abuse, Hospitalization, Psychiatry and Mental health, Family medicine, Female, Thematic analysis, business, Neonatal Abstinence Syndrome, Qualitative research, Buprenorphine, medicine.drug
Abstract: OBJECTIVES Understanding the experience of parents with newborns hospitalized with neonatal abstinence syndrome (NAS) across all inpatient settings is important in optimizing their involvement as part of the care team. A descriptive qualitative study design was utilized to understand the parental experience and identify barriers to parent involvement in care of newborns with NAS care. METHODS Semistructured one-on-one interviews were conducted with parents of a convenience sample of fifteen infants admitted for NAS in the newborn nursery and level II/III neonatal intensive care unit within a tertiary care center in Northern New England. Interviews were analyzed using thematic content analysis. RESULTS Sixty percent of mothers were treated with buprenorphine during pregnancy, and 60% of infants required pharmacological treatment for NAS symptoms. The predominant themes of parental experience included preparation/education for hospitalization, communication with providers, NAS management, family resources, physical hospital environment, and maternal guilt. CONCLUSION The parental experience of care for NAS is negatively affected by lack of standardized NAS education in the prenatal and postnatal settings, inconsistent communication with providers, the Finnegan scoring system, lack of provider sensitivity to parental substance use disorder, and maternal guilt. This study also highlights the parental desire to be more involved in the care of newborns with NAS.
Published: 2020

45. Seroma after Simple Mastectomy in Breast Cancer—The Role of CD4+ T Helper Cells and the Evidence as a Possible Specific Immune Process

Author: Nicole Pochert, Mariella Schneider, Nadine Ansorge, Annamarie Strieder, Jacqueline Sagasser, Matthias Reiger, Claudia Traidl-Hoffmann, Avidan Neumann, Udo Jeschke, Christian Dannecker, Thorsten Kühn, and Nina Ditsch
Subjects: Organic Chemistry, Immunity, Article, breast cancer, simple mastectomy, seroma formation, lymphocyte enrichment, T-helper cells, Th2 cells, Th17 cells, Breast Neoplasms, Pilot Projects, General Medicine, Catalysis, ddc, Computer Science Applications, Inorganic Chemistry, Postoperative Complications, Seroma, Th2 Cells, Humans, Th17 Cells, Female, ddc:610, Physical and Theoretical Chemistry, Molecular Biology, Mastectomy, Spectroscopy, Mastectomy, Simple
Abstract: Seroma development after breast cancer surgery is the most common postoperative complication seen after mastectomy but neither its origin nor its cellular composition is known. To investigate the assumption of immunological significance, one of the first aims of this pilot study is to describe the cellular content of collected seroma fluids and its corresponding serum in patients with simple mastectomy after needle aspiration, as well as the serum of healthy controls. The content of red blood cells (RBC) was measured by haemato-counter analyses, and the lymphocyte identification/quantification was conducted by flow cytometry analyses in seroma fluid (SFl) and the sera of patients (PBp) as well as controls (PBc). Significantly lower numbers of RBCs were measured in SFl. Cytotoxic T cells are significantly reduced in SFl, whereas T helper (Th) cells are significantly enriched compared to PBp. Significantly higher numbers of Th2 cells were found in SFl and PBp compared to PBc. The exact same pattern is seen when analyzing the Th17 subgroup. In conclusion, in contrast to healthy controls, significantly higher Th2 and Th17 cell subgroup-mediated immune responses were measured in seroma formations and were further confirmed in the peripheral blood of breast cancer (including DCIS) patients after simple mastectomy. This could lead to the assumption of a possible immunological cause for the origin of a seroma.
Published: 2022
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46. Association of a Perioperative Multicomponent Fall Prevention Intervention With Falls and Quality of Life After Elective Inpatient Surgical Procedures

Author: Bradley A, Fritz, Christopher R, King, Divya, Mehta, Emily, Somerville, Alex, Kronzer, Arbi, Ben Abdallah, Troy, Wildes, Michael S, Avidan, Eric J, Lenze, Susan, Stark, and Jennifer, Tappenden
Subjects: Cohort Studies, Male, Inpatients, Elective Surgical Procedures, Quality of Life, Humans, Accidental Falls, Female, Prospective Studies, General Medicine, Middle Aged, Aged
Abstract: Falls after elective inpatient surgical procedures are common and have physical, emotional, and financial consequences. Close interactions between patients and health care teams before and after surgical procedures may offer opportunities to address modifiable risk factors associated with falls.To assess whether a multicomponent intervention that incorporates education, home medication review, and home safety assessment is associated with reductions in the incidence of falls after elective inpatient surgical procedures.This prospective propensity score-matched cohort study was a prespecified secondary analysis of data from the Electroencephalography Guidance of Anesthesia to Alleviate Geriatric Syndromes (ENGAGES) randomized clinical trial, which was conducted at a single academic medical center between January 16, 2015, and May 7, 2018. Patients in the intervention group of the present study were enrolled in either arm of the ENGAGES clinical trial. Patients in the control group were selected from the Systematic Assessment and Targeted Improvement of Services Following Yearly Surgical Outcomes Surveys prospective observational cohort study, which created a registry of patient-reported postoperative outcomes at the same single center. The propensity score-matched cohort in the present study included 1396 patients (698 pairs) selected from a pool of 2013 eligible patients. All patients underwent elective surgical procedures with general anesthesia and had a hospital stay of 2 or more days. Data were analyzed from January 2, 2020, to January 11, 2022.The multicomponent safety intervention (offered to all patients in the ENGAGES clinical trial) included patient education on fall prevention techniques, home medication review by a geriatric psychiatrist (with communication of recommended changes to the surgeon), a self-administered home safety assessment, and targeted occupational therapy home visits with home hazard removal (offered to patients with a preoperative history of falls).The primary outcome was patient-reported falls within 1 year after an elective inpatient surgical procedure. The secondary outcome was quality of life 1 year after an elective surgical procedure, which was measured using the physical and mental composite summary scores on the Veterans RAND 12-item health survey (score range, 0-100 points, with 0 indicating lowest quality of life and 100 indicating highest quality of life).Among 1396 patients, the median age was 69 years (IQR, 64-75 years), and 739 patients (52.9%) were male. With regard to race, 5 patients (0.4%) were Asian, 97 (6.9%) were Black or African American, 2 (0.1%) were Native Hawaiian or Pacific Islander, 1237 (88.6%) were White, 3 (0.2%) were of other race, and 52 (3.7%) were of unknown race; with regard to ethnicity, 12 patients (0.9%) were Hispanic or Latino, 1335 (95.6%) were non-Hispanic or non-Latino, and 49 (3.5%) were of unknown ethnicity. Adherence to individual intervention components was modest (from 22.9% for completion of the self-administered home safety assessment to 28.2% for implementation of the geriatric psychiatrist's recommended medication changes). Falls within 1 year after surgical procedures were reported by 228 of 698 patients (32.7%) in the intervention group and 225 of 698 patients (32.2%) in the control group. No significant difference was found in falls between the 2 groups (standardized risk difference, 0.4%; 95% CI, -4.5% to 5.3%). After adjusting for preoperative quality of life, patients in the intervention group had higher physical composite summary scores (3.8 points; 95% CI, 2.4-5.1 points) and higher mental composite summary scores (5.7 points; 95% CI, 4.7-6.7 points) at 1 year compared with patients in the control group.In this cohort study, a multicomponent safety intervention was not associated with reductions in falls within the first year after an elective surgical procedure; however, an increase in quality of life at 1 year was observed. These results suggest a need for other interventions, such as those designed to increase adherence, to lower the incidence of falls after surgical procedures.
Published: 2022
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47. Intraoperative ketamine for prevention of depressive symptoms after major surgery in older adults: an international, multicentre, double-blind, randomised clinical trial

Author: Eric J. Lenze, Robert A. Veselis, Phillip E. Vlisides, A. Ben Abdallah, Renée El-Gabalawy, Kane O. Pryor, Michael S. Avidan, George A. Mashour, Eric Jacobsohn, and Hannah R. Maybrier
Subjects: Male, 0301 basic medicine, medicine.medical_specialty, Health Status, Placebo, Intraoperative Period, 03 medical and health sciences, 0302 clinical medicine, Neuroscience and Neuroanaesthesia, Double-Blind Method, Surveys and Questionnaires, History of depression, Humans, Medicine, Ketamine, General anaesthesia, Depression (differential diagnoses), Aged, Anesthetics, Dissociative, Depression, business.industry, Age Factors, Middle Aged, Confidence interval, Surgery, Clinical trial, 030104 developmental biology, Anesthesiology and Pain Medicine, Socioeconomic Factors, Surgical Procedures, Operative, Cohort, Female, business, 030217 neurology & neurosurgery, medicine.drug
Abstract: Background Ketamine is a general anaesthetic with anti-depressant effects at subanaesthetic doses. We hypothesised that intraoperative administration of ketamine would prevent or mitigate postoperative depressive symptoms in surgical patients. Methods We conducted an international, randomised clinical trial testing the effects of intraoperative administration of ketamine [0.5 mg kg−1 (Lo-K) or 1.0 mg kg−1 (Hi-K)] vs control [saline placebo (P)] in patients ≥60 yr old undergoing major surgery with general anaesthesia. We administered the Patient Health Questionnaire-8 before the operation, on postoperative day (POD) 3 (primary outcome), and on POD30 to assess depressive symptoms, a secondary outcome of the original trial. Results There was no significant difference on POD3 in the proportion of patients with symptoms suggestive of depression between the placebo [23/156 (14.7%)] and combined ketamine (Lo-K plus Hi-K) [61/349 (17.5%)] groups [difference = –2.7%; 95% confidence interval (CI), 5.0% to –9.4%; P=0.446]. Of the total cohort, 9.6% (64/670; 95% CI, 7.6–12.0%) had symptoms suggestive of depression before operation, which increased to 16.6% (84/505; 95% CI, 13.6–20.1%) on POD3, and decreased to 11.9% (47/395; 95% CI, 9.1–15.5%) on POD30. Of the patients with depressive symptoms on POD3 and POD30, 51% and 49%, respectively, had no prior history of depression or depressive symptoms. Conclusions Major surgery is associated with new-onset symptoms suggestive of depression in patients ≥60 yr old. Intraoperative administration of subanaesthetic ketamine does not appear to prevent or improve depressive symptoms. Clinical trials registration NCT01690988.
Published: 2018
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48. Frailty Phenotypes and Relations With Surgical Outcomes

Author: Anshuman Sharma, Daniel L. Helsten, Arbi Ben Abdallah, Sherry L. McKinnon, Michael S. Avidan, Troy S. Wildes, Furqaan Sadiq, Lawrence M. Scheier, and Vanessa L. Kronzer
Subjects: Adult, Male, Gerontology, Activities of daily living, Frail Elderly, Emotions, Nutritional Status, Patient Readmission, Risk Assessment, Severity of Illness Index, Article, 03 medical and health sciences, Postoperative Complications, 0302 clinical medicine, Predictive Value of Tests, Risk Factors, Activities of Daily Living, Severity of illness, Humans, Medicine, Patient Reported Outcome Measures, Registries, 030212 general & internal medicine, Social Behavior, Geriatric Assessment, Aged, Retrospective Studies, Frailty, business.industry, Age Factors, Geriatric assessment, Retrospective cohort study, Middle Aged, Mental health, Phenotype, Latent class model, Mental Health, Treatment Outcome, Anesthesiology and Pain Medicine, Physical Fitness, Surgical Procedures, Operative, Quality of Life, Female, Observational study, business, 030217 neurology & neurosurgery
Abstract: BACKGROUND: Frailty is an important concept in the care of older adults although controversy remains regarding its defining features and clinical utility. Both the Fried phenotype and the Rockwood deficit accumulation approaches cast frailty as a “burden” without exploring the relative salience of its cardinal markers and their relevance to the patient. New multifactorial perspectives require a reliable assessment of frailty that can validly predict postoperative health outcomes. METHODS: In a retrospective study of 2,828 unselected surgical patients, we used item response theory to examine the ability of 32 heterogeneous markers capturing limitations in physical, functional, emotional, and social activity domains to indicate severity of frailty as a latent continuum. Eighteen markers efficiently indicated frailty severity and were then subject to latent class analysis to derive discrete phenotypes. Next, we validated the obtained frailty phenotypes against patient-reported 30-day postoperative outcomes using multivariable logistic regression. Models were adjusted for demographics, comorbidity, type and duration of surgery, and cigarette and alcohol consumption. RESULTS: The 18 markers provided psychometric evidence of a single reliable continuum of frailty severity. Latent class analyses produced three distinct subtypes, based on patients’ endorsement probabilities of the frailty indicators: Not Frail (49.7%), Moderately Frail (33.5%), and Severely Frail (16.7%). Unlike the Moderate class, Severely Frail endorsed emotional health problems in addition to physical burdens and functional limitations. Models adjusting for age, sex, type of anesthesia, as well as intra-operative factors indicated that Severely Frail (OR =1.89, 95% CI =1.42 to 2.50) and Moderately Frail patients (OR =1.31, 95% CI =1.03 to 1.67) both had higher odds of experiencing postoperative complications compared to Not Frail patients. In a three-way comparison, a higher proportion of Severely Frail patients (10.7%) reported poorer quality of life after surgery compared to Moderately Frail (9.2%) and Not Frail (8.3%) patients (p
Published: 2018
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49. Intraoperative electroencephalogram suppression at lower volatile anaesthetic concentrations predicts postoperative delirium occurring in the intensive care unit

Author: Michael S. Avidan, Hannah R. Maybrier, and Bradley A. Fritz
Subjects: Adult, Male, Adolescent, Critical Care, law.invention, Cohort Studies, Young Adult, 03 medical and health sciences, Consciousness Monitors, Emergence Delirium, 0302 clinical medicine, Predictive Value of Tests, 030202 anesthesiology, law, mental disorders, medicine, Humans, Elective surgery, Aged, Retrospective Studies, Aged, 80 and over, business.industry, Incidence, Medical record, Electroencephalography, Retrospective cohort study, Odds ratio, Middle Aged, Intensive care unit, Confidence interval, Intensive Care Units, Anesthesiology and Pain Medicine, Anesthesia, Anesthetics, Inhalation, Delirium, Female, medicine.symptom, Complication, business, Algorithms, 030217 neurology & neurosurgery, Research Article
Abstract: BACKGROUND: Postoperative delirium is a common complication associated with increased morbidity and mortality. A recently-reported association between intraoperative electroencephalogram suppression and postoperative delirium might be mediated in some patients by a heightened sensitivity to volatile anaesthetics. METHODS: This retrospective cohort study included 618 elective surgery patients with planned intensive care unit admission, who also received intraoperative electroencephalogram monitoring and had delirium assessments documented in the medical record. Sensitivity to volatile anaesthetics was assessed using a mixed effects model predicting the likelihood of electroencephalogram suppression at each time point based on the current end-tidal anaesthetic concentration. Patients with a random intercept above the population median (electroencephalogram suppression at lower anaesthetic concentrations) were classified as having heightened sensitivity to volatile anaesthetics. Delirium was defined as a positive Confusion Assessment Method for the Intensive Care Unit assessment anytime in the first five postoperative days. RESULTS: Postoperative delirium was observed in 162 of 618 patients (26%). Patients who experienced electroencephalogram suppression at lower volatile anaesthetic concentrations had a higher incidence of postoperative delirium [109/309 (35%)] than other patients [53/309 (17%)] [unadjusted odds ratio 2.63; 95% confidence interval (CI), 1.81–3.84, P
Published: 2018
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50. Visual Aversive Learning Compromises Sensory Discrimination

Author: Rony Paz, Lee Shalev, and Galia Avidan
Subjects: Adult, Male, 0301 basic medicine, genetic structures, Brain activity and meditation, media_common.quotation_subject, Reflex, Pupillary, Young Adult, 03 medical and health sciences, Discrimination, Psychological, 0302 clinical medicine, Perception, Avoidance Learning, medicine, Humans, Fear conditioning, Research Articles, Anterior cingulate cortex, Visual Cortex, media_common, Cerebral Cortex, Brain Mapping, General Neuroscience, Amygdala, Anxiety Disorders, Magnetic Resonance Imaging, 030104 developmental biology, Visual cortex, medicine.anatomical_structure, Acoustic Stimulation, Auditory Perception, Visual Perception, Female, Aversive Stimulus, Psychology, Visual learning, Neuroscience, Insula, Photic Stimulation, Psychomotor Performance, 030217 neurology & neurosurgery
Abstract: Aversive learning is thought to modulate perceptual thresholds, which can lead to overgeneralization. However, it remains undetermined whether this modulation is domain specific or a general effect. Moreover, despite the unique role of the visual modality in human perception, it is unclear whether this aspect of aversive learning exists in this modality. The current study was designed to examine the effect of visual aversive outcomes on the perception of basic visual and auditory features. We tested the ability of healthy participants, both males and females, to discriminate between neutral stimuli, before and after visual learning. In each experiment, neutral stimuli were associated with aversive images in an experimental group and with neutral images in a control group. Participants demonstrated a deterioration in discrimination (higher discrimination thresholds) only after aversive learning. This deterioration was measured for both auditory (tone frequency) and visual (orientation and contrast) features. The effect was replicated in five different experiments and lasted for at least 24 h. fMRI neural responses and pupil size were also measured during learning. We showed an increase in neural activations in the anterior cingulate cortex, insula, and amygdala during aversive compared with neutral learning. Interestingly, the early visual cortex showed increased brain activity during aversive compared with neutral context trials, with identical visual information. Our findings imply the existence of a central multimodal mechanism, which modulates early perceptual properties, following exposure to negative situations. Such a mechanism could contribute to abnormal responses that underlie anxiety states, even in new and safe environments.SIGNIFICANCE STATEMENTUsing a visual aversive-learning paradigm, we found deteriorated discrimination abilities for visual and auditory stimuli that were associated with visual aversive stimuli. We showed increased neural activations in the anterior cingulate cortex, insula, and amygdala during aversive learning, compared with neutral learning. Importantly, similar findings were also evident in the early visual cortex during trials with aversive/neutral context, but with identical visual information. The demonstration of this phenomenon in the visual modality is important, as it provides support to the notion that aversive learning can influence perception via a central mechanism, independent of input modality. Given the dominance of the visual system in human perception, our findings hold relevance to daily life, as well as imply a potential etiology for anxiety disorders.
Published: 2018
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